Carboxylic acid amides, the preparation thereof, and their use as pharmaceutical compositions

ABSTRACT

The present invention relates to new substituted carboxylic acid amides of general formula  
                 
 
     wherein A, B and R 1  to R 5  are defined as in claim 1, the tautomers, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, which have valuable properties.  
     The compounds of the above general formula I as well as the tautomers, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, and their stereoisomers have valuable pharmacological properties, particularly an antithrombotic activity and a factor Xa-inhibiting activity.

[0001] The present invention relates to new substituted carboxylic acid amides of general formula

[0002] the tautomers, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, which have valuable properties.

[0003] The compounds of the above general formula I as well as the tautomers, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof, particularly the physiologically acceptable salts thereof with inorganic or organic acids or bases, and their stereoisomers have valuable pharmacological properties, particularly an antithrombotic activity and a factor Xa-inhibiting activity.

[0004] The present application thus relates to the new compounds of the above general formula 1, the preparation thereof, the pharmaceutical compositions containing the pharmacologically effective compounds, the preparation thereof and their use.

[0005] In the above general formula I

[0006] R¹ denotes an amino, C₁₋₅-alkylamino, C₃₋₇-cycloalkylamino or (phenyl-C₁₋₃-alkyl)-amino group which may be substituted in each case at the amino nitrogen atom by a phenylcarbonyl or phenylsulphonyl group or by a C₁₋₅-alkyl or C₁₋₅-alkylcarbonyl group optionally substituted in the alkyl moiety by a carboxy group, a group which may be converted into a carboxy group in vivo, an amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or C₃₋₆-cycloalkyleneimino group, while two nitrogen atoms are separated from one another by at least two carbon atoms,

[0007] a di-(C₁₋₅-alkyl)amino or N—(C₃₋₇-cycloalkyl)-C₁₋₅-alkylamino group, while the C₁₋₅-alkyl moiety with the exception of the 1 position may be substituted in each case by a hydroxy, C₁₋₃-alkoxy, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or C₃₋₆-cycloalkyleneimino group,

[0008] a 4- to 7-membered cycloalkyleneiminocarbonyl or cycloalkyleneiminosulphonyl group, while

[0009] the cycloalkyleneimino moiety may be substituted by one or two C₁₋₃-alkyl, C₁₋₃-alkoxy-C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₁₋₅-alkyloxycarbonylamino-C₁₋₃-alkyl, C₃₋₆-cycloalkylamino-C₁₋₃-alkyl, aminocarbonyl, C₁₋₃-alkylamino-carbonyl, N—(C₃₋₇-cycloalkyl)-C₁₋₅-alkylaminocarbonyl, N-(phenyl-C₁₋₃-alkyl)-C₁₋₅-alkylaminocarbonyl or di-(C₁₋₃-alkyl)-aminocarbonyl group or

[0010] a methylene group not adjacent to the imino group may be substituted by a hydroxy, benzyloxy, C₁₋₃-alkoxy, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or C₃₋₆-cycloalkyleneimino group and/or

[0011] a methylene group in the 3 position of a 5-membered cycloalkyleneimino group may be replaced by a sulphur atom, a sulphinyl or sulphonyl group or

[0012] a methylene group in the 4 position of a 6- or 7-membered cycloalkyleneimino group may be replaced by an oxygen or sulphur atom or by an —NH—, —N—C₁₋₃-alkyl-, —N(C₂₋₃-alkanoyl)-, sulphinyl or sulphonyl group and/or

[0013] a —CH₂—CH₂— group in a 5- to 7-membered cycloalkyleneimino group may be replaced by an —NH—CO—, —CO—NH—, —CO—N(CH₃)— or a —N(CH₃)—CO-group,

[0014] a 5- to 7-membered cycloalkenyleneiminocarbonyl or cycloalkenyleneiminosulphonyl group optionally substituted by one or two C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl, C₁₋₆-cycloalkylamino-C₁₋₃-alkyl, aminocarbonyl, C₁₋₃-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl or C₃₋₆-cycloalkyleneiminocarbonyl groups, while the double bond is not bound to a nitrogen atom,

[0015] an aminocarbonyl or aminosulphonyl group optionally substituted by one or two C₁₋₅-alkyl groups,

[0016] while the substituents may be identical or different and

[0017] in each case one of the C₁₋₅-alkyl groups may be substituted by one or two C₁₋₃-alkyl, C₁₋₃-alkoxy-C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl, C₁₋₅-alkyloxycarbonylamino-C₁₋₃-alkyl, C₃₋₆-cycloalkylamino-C₁₋₃-alkyl, aminocarbonyl, C₁₋₃-alkylamino-carbonyl, N—(C₃₋₇-cycloalkyl)-C₁₋₅-alkylaminocarbonyl, N-(phenyl-C₁₋₃-alkyl)-C₁₋₅-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl or C₃₋₆-cycloalkyleneiminocarbonyl group or

[0018] a methylene group not adjacent to the imino group may be substituted by a hydroxy, benzyloxy, C₁₋₃-alkoxy, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or C₃₋₆-cycloalkyleneimino group,

[0019] a C₁₋₇-alkylcarbonyl or C₃₋₇-cycloalkylcarbonyl group, while

[0020] the methylene group in the 2, 3 or 4 position in a C₃₋₇-cycloalkylcarbonyl group may be replaced by an oxygen or sulphur atom, a carbonyl, sulphinyl, sulphonyl or an —NH— group, wherein

[0021] the hydrogen atom of the —NH— group may be replaced by a C₁₋₃-alkyl or C₁₋₃-alkyl-carbonyl group,

[0022] a phenylcarbonyl or heteroarylcarbonyl group which may be substituted in the phenyl or heteroaryl moiety by a fluorine, chlorine or bromine atom, by a trifluoromethyl, C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl or C₁₋₃-alkoxy group,

[0023] a C₁₋₃-alkyl group optionally monosubstituted by an amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, hydroxy, phenyl, heteroaryl or a 4- to 7-membered cycloalkyleneimino group, while

[0024] the phenyl moiety may be substituted by a fluorine, chlorine or bromine atom, by a trifluoromethyl, C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl or C₁₋₃-alkoxy group and/or

[0025] a —CH₂—CH₂— group in a 5- to 7-membered cycloalkyleneimino group may be replaced by an —NH—CO—, —CO—NH—, —CO—N(CH₃)— or a —N(CH₃)—CO—group or

[0026] a methylene group, which is adjacent to the nitrogen atom, in a 5- to 7-membered cycloalkyleneimino group may be replaced by a carbonyl group,

[0027] or a group of formula

[0028] wherein in the heterocyclic moiety in each case a hydrogen atom may be replaced by a methylsulphonylmethyl, amino-C₁₋₃-alkyl or aminocarbonyl group and

[0029] m denotes the number 1 or 2,

[0030] R² denotes a hydrogen, fluorine, chlorine or bromine atom, a C₁₋₃-alkyl group wherein the hydrogen atoms may be wholly or partly replaced by fluorine atoms, a C₂₋₃-alkenyl, C₂₋₃-alkynyl, C₁₋₃-alkoxy or trifluoromethoxy group,

[0031] R³ denotes a hydrogen atom or a C₁₋₃-alkyl group,

[0032] R⁴ denotes a hydrogen atom or a straight-chain or branched C₁₋₅-alkyl group which is optionally substituted by a hydroxy, C₁₋₃-alkyloxy, mercapto, C₁₋₃-alkylsulphanyl, C₁₋₃-alkylsulphinyl, C₁₋₃-alkylsulphonyl, carboxy, aminocarbonyl, C₁₋₃-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl, C₃₋₆-cycloalkyleneiminocarbonyl, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, C₃₋₆-cycloalkyleneimino, C₁₋₃-alkylcarbonylamino, C₃₋₆-cycloalkylcarbonylamino, benzyloxycarbonylamino or guanidino group,

[0033] a phenyl or heteroaryl, phenyl-C₁₋₃-alkyl or heteroaryl-C₁₋₃-alkyl group which is optionally substituted by a hydroxy, C₁₋₄-alkyloxy, benzyloxy, hydroxycarbonyl-C₁₋₃-alkoxy, C₁₋₃-alkyloxycarbonyl-C₁₋₃-alkyloxy, aminocarbonyl-C₁₋₃-alkyloxy, C₁₋₃-alkylaminocarbonyl-C₁₋₃-alkyloxy, di-(C₁₋₃-alkyl)-aminocarbonyl-C₁₋₃-alkyloxy, C₃₋₆-cycloalkyleneiminocarbonyl-C₁₋₃-alkoxy, carboxy, C₁₋₃-alkyloxycarbonyl group,

[0034] a 4- to 7-membered cycolalkyleneimino-C₁₋₃-alkyl group or

[0035] a 4- to 7-membered cycloalkyl-C₁₋₃-alkyl group wherein one or two methylene groups may be replaced by an —NH— or —N(C₁₋₃-alkyl)- group and wherein one or two methylene groups adjacent to the —NH— or —N(C₁₋₃-alkyl)- group may each be replaced by a carbonyl group, with the proviso that a cycloalkyl group as hereinbefore defined wherein two —NH— or —N(C₁₋₃-alkyl)- groups are separated from one another by precisely one —CH₂— group are excluded,

[0036] R⁵ denotes a hydrogen atom or a C₁₋₃-alkyl group or

[0037] R⁴ and R⁵ together with the carbon atom to which they are bound, denote a C₃₋₇-cycloalkyl group, while

[0038] one of the methylene groups of the C₃₋₇-cycloalkyl group may be replaced by an imino, C₁₋₃-alkylimino, acylimino or sulphonylimino group,

[0039] A denotes a carbonylamino or aminocarbonyl group, while the hydrogen atom of the amino function may optionally be substituted by a C₁₋₃-alkyl group, and

[0040] B denotes a group of formula

[0041]  wherein

[0042] n denotes the number 1 or 2,

[0043] R⁶ denotes a hydrogen atom or a C₁₋₃-alkyl, hydroxy, amino, C₁₋₃-alkylamino group and

[0044] R⁷ denotes a hydrogen, fluorine, chlorine or bromine atom, a C₁₋₃-alkyl group wherein the hydrogen atoms may be wholly or partly replaced by fluorine atoms, a C₂₋₃-alkenyl or C₂₋₃-alkynyl, a hydroxy, C₁₋₃-alkoxy, trifluoromethoxy or cyano group,

[0045] while, unless otherwise stated, by the phrase “heteroaryl group” is meant a monocyclic 5- or 6-membered heteroaryl group optionally substituted in the carbon skeleton by a C₁₋₃-alkyl, carboxy, C₁₋₃-alkoxy-carbonyl or C₁₋₃-alkoxycarbonylamino group, while

[0046] the 6-membered heteroaryl group contains one, two or three nitrogen atoms and

[0047] the 5-membered heteroaryl group contains an imino group optionally substituted by a C₁₋₃-alkyl or phenyl-C₁₋₃-alkyl group, or an oxygen or sulphur atom or

[0048] an imino group optionally substituted by a C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl or phenyl-C₁₋₃-alkyl group, or an oxygen or sulphur atom and additionally a nitrogen atom or

[0049] an imino group optionally substituted by a C₁₋₃-alkyl or phenyl-C₁₋₃-alkyl group and two or three nitrogen atoms,

[0050] and also a phenyl ring may be fused to the above-mentioned monocyclic heteroaryl groups via two adjacent carbon atoms

[0051] and the bond is effected via a nitrogen atom or via a carbon atom of the heterocyclic moiety or a fused-on phenyl ring,

[0052] while unless otherwise stated the alkyl and alkoxy groups contained in the definitions which have more than two carbon atoms may be straight-chain or branched,

[0053] and the hydrogen atoms of the methyl or ethyl groups contained in the definitions may be wholly or partly replaced by fluorine atoms.

[0054] Among the embodiments referred to above, particular importance is attached to those compounds of general formula I wherein R³ denotes the hydrogen atom.

[0055] By a group which may be converted in vivo into a carboxy group is meant for example a carboxy group esterified with an alcohol wherein the alcohol moiety is preferably a C₁₋₆-alkanol, a phenyl-C₁₋₃-alkanol, a C₃₋₉-cycloalkanol, a C₅₋₇-cycloalkenol, a C₃₋₅-alkenol, a phenyl-C₃₋₅-alkenol, a C₃₋₅-alkynol or phenyl-C₃₋₅-alkynol, with the proviso that no bond to the oxygen atom starts from a carbon atom which carries a double or triple bond, a C₃₋₈-cycloalkyl-C₁₋₃-alkanol or an alcohol of formula

R⁸—CO—O—(R⁹CR¹⁰)—OH,

[0056]  wherein

[0057] R⁸ denotes a C₁₋₈-alkyl, C₅₋₇-cycloalkyl, phenyl or phenyl-C₁₋₃-alkyl group,

[0058] R⁹ denotes a hydrogen atom, a C₁₋₃-alkyl, C₅₋₇-cycloalkyl or phenyl group and R¹⁰ denotes a hydrogen atom or a C₁₋₃-alkyl group.

[0059] Preferred groups which may be cleaved from a carboxy group in vivo include a C₁₋₆-alkoxy group such as the methoxy, ethoxy, n-propyloxy, isopropyloxy, n-butyloxy, n-pentyloxy, n-hexyloxy or cyclohexyloxy group or a phenyl-C₁₋₃-alkoxy group such as the benzyloxy group.

[0060] Those compounds of general formula I wherein R¹ contains a group which may be converted in vivo into a carboxy group are prodrugs for those compounds of general formula I wherein R¹ contains a carboxy group.

[0061] Preferred compounds of general formula I are those wherein

[0062] R¹ denotes an amino, C₁₋₅-alkylamino, C₃₋₇-cycloalkylamino or (phenyl-C₁₋₃-alkyl)-amino group which may be substituted in each case at the amino nitrogen atom by a phenylcarbonyl or phenylsulphonyl group or by a C₁₋₅-alkyl or C₁₋₅-alkylcarbonyl group optionally substituted in the alkyl moiety by a carboxy group, a group which may be converted into a carboxy group in vivo, an amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or C₃₋₆-cycloalkyleneimino group, while two nitrogen atoms are separated from one another by at least two carbon atoms,

[0063] a di-(C₁₋₅-alkyl)amino or N—(C₃₋₇-cycloalkyl)-C₁₋₅-alkylamino group, while the C₁₋₅-alkyl moiety with the exception of the 1 position may be substituted in each case by a hydroxy, C₁₋₃-alkoxy, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or C₃₋₆-cycloalkyleneimino group,

[0064] a 4- to 7-membered cycloalkyleneiminocarbonyl or cycloalkyleneiminosulphonyl group, while

[0065] the cycloalkyleneimino moiety may be substituted by one or two C₁₋₃-alkyl, C₁₋₃-alkoxy-C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl, C₁₋₅-alkyloxycarbonylamino-C₁₋₃-alkyl, C₃₋₆-cycloalkylamino-C₁₋₃-alkyl, aminocarbonyl, C₁₋₃-alkylaminocarbonyl, N—(C₃₋₇-cycloalkyl)-C₁₋₅-alkylaminocarbonyl, N-(phenyl-C₁₋₃-alkyl)-C₁₋₅-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl or C₃₋₆-cycloalkyleneiminocarbonyl group or

[0066] a methylene group not adjacent to the imino group may be substituted by a hydroxy, benzyloxy, C₁₋₃-alkoxy, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or C₃₋₆-cycloalkyleneimino group and/or

[0067] a methylene group in the 3 position of a 5-membered cycloalkyleneimino group by may be replaced a sulphur atom, a sulphinyl or sulphonyl group or

[0068] a methylene group in the 4 position of a 6- or 7-membered cycloalkyleneimino group may be replaced by an oxygen or sulphur atom or by an —NH—, —N—C₁₋₃-alkyl-, —N(C₂₋₃-alkanoyl)-, sulphinyl or sulphonyl group and/or

[0069] a —CH₂—CH₂— group in a 5- to 7-membered cycloalkyleneimino group may be replaced by an —NH—CO—, —CO—NH—, —CO—N(CH₃)— or a —N(CH₃)—CO-group,

[0070] a 5- to 7-membered cycloalkenyleneiminocarbonyl or cycloalkenyleneiminosulphonyl group optionally substituted by one or two C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl, C₁₋₆-cycloalkylamino-C₁₋₃-alkyl, aminocarbonyl, C₁₋₃-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl or C₃₋₆-cycloalkyleneiminocarbonyl groups, while the double bond is not bound to a nitrogen atom,

[0071] an aminocarbonyl or aminosulphonyl group optionally substituted by one or two C₁₋₅-alkyl groups,

[0072] while the substituents may be identical or different and in each case one of the C₁₋₅-alkyl groups may be substituted by one or two C₁₋₃-alkyl, C₁₋₃-alkoxy-C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl, C₁₋₅-alkyloxycarbonylamino-C₁₋₃-alkyl, C₃₋₆-cycloalkylamino-C₁₋₃-alkyl, aminocarbonyl, C₁₋₃-alkylamino-carbonyl, N—(C₃₋₇-cycloalkyl)-C₁₋₅-alkylaminocarbonyl, N-(phenyl-C₁₋₃-alkyl)-C₁₋₅-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl or C₃₋₆-cycloalkyleneiminocarbonyl group or

[0073] a methylene group not adjacent to the imino group may be substituted by a hydroxy, benzyloxy, C₁₋₃-alkoxy, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or C₃₋₆-cycloalkyleneimino group,

[0074] a C₁₋₇-alkylcarbonyl or C₃₋₇-cycloalkylcarbonyl group, while

[0075] the methylene group in the 2, 3 or 4 position in a C₃₋₇-cycloalkylcarbonyl group may be replaced by an oxygen or sulphur atom, a carbonyl, sulphinyl, sulphonyl or an —NH— group, wherein

[0076] the hydrogen atom of the —NH— group may be replaced by a C₁₋₃-alkyl or C₁₋₃-alkyl-carbonyl group,

[0077] a phenylcarbonyl or heteroarylcarbonyl group which may be substituted in the phenyl or heteroaryl moiety by a fluorine, chlorine or bromine atom, by a trifluoromethyl, C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl or C₁₋₃-alkoxy group,

[0078] a C₁₋₃-alkyl group optionally monosubstituted by an amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, hydroxy, phenyl, heteroaryl or a 4- to 7-membered cycloalkyleneimino group, while

[0079] the phenyl moiety may be substituted by a fluorine, chlorine or bromine atom, by a trifluoromethyl, C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl or C₁₋₃-alkoxy group and/or

[0080] a —CH₂—CH₂— group in a 5- to 7-membered cycloalkyleneimino group may be replaced by an —NH—CO—, —CO—NH—, —CO—N(CH₃)— or a —N(CH₃)—CO—group or

[0081] a methylene group, which is adjacent to the nitrogen atom, in a 5- to 7-membered cycloalkyleneimino group may be replaced by a carbonyl group,

[0082] or a group of formula

[0083] wherein in the heterocyclic moiety a hydrogen atom may be replaced in each case by a methylsulphonylmethyl, amino-C₁₋₃-alkyl or aminocarbonyl group and

[0084] m denotes the number 1 or 2,

[0085] R² denotes a chlorine or bromine atom, a C₁₋₃-alkyl group wherein the hydrogen atoms may be wholly or partly replaced by fluorine atoms, or a C₂₋₃-alkenyl group,

[0086] R³ denotes a hydrogen atom or a C₁₋₃-alkyl group,

[0087] R⁴ denotes a hydrogen atom or a straight-chain or branched C₁₋₅-alkyl group which is optionally substituted by a hydroxy, C₁₋₃-alkyloxy, mercapto, C₁₋₃-alkylsulphanyl, C₁₋₃-alkylsulphinyl, C₁₋₃-alkylsulphonyl, carboxy, aminocarbonyl, C₁₋₃-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl, C₃₋₆-cycloalkyleneiminocarbonyl, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, C₃₋₆-cycloalkyleneimino, C₁₋₃-alkylcarbonylamino, C₃₋₆-cycloalkylcarbonylamino, benzyloxycarbonylamino or guanidino group,

[0088] a phenyl or heteroaryl, phenyl-C₁₋₃-alkyl or heteroaryl-C₁₋₃-alkyl group which is optionally substituted by a hydroxy, C₁₋₄-alkyloxy, benzyloxy, hydroxycarbonyl-C₁₋₃-alkoxy, C₁₋₃-alkyloxycarbonyl-C₁₋₃-alkyloxy, aminocarbonyl-C₁₋₃-alkyloxy, C₁₋₃-alkylaminocarbonyl-C₁₋₃-alkyloxy, di-(C₁₋₃-alkyl)-aminocarbonyl-C₁₋₃-alkyloxy, C₃₋₆-cycloalkyleneiminocarbonyl-C₁₋₃-alkoxy, carboxy, C₁₋₃-alkyloxycarbonyl group,

[0089] a 4- to 7-membered cycolalkyleneimino-C₁₋₃-alkyl group or

[0090] a 4- to 7-membered cycloalkyl-C₁₋₃-alkyl group wherein one or two methylene groups may be replaced by an —NH— or —N(C₁₋₃-alkyl)- group and wherein one or two methylene groups adjacent to the —NH— or —N(C₁₋₃-alkyl)- group may each be replaced by a carbonyl group, with the proviso that a cycloalkyl group as hereinbefore defined wherein two —NH— or —N(C₁₋₃-alkyl)- groups are separated from one another by precisely one —CH₂— group are excluded,

[0091] R⁵ denotes a hydrogen atom or a C₁₋₃-alkyl group or

[0092] R⁴ and R⁵ together with the carbon atom to which they are bound denote a C₃₋₇-cycloalkyl group, while

[0093] one of the methylene groups of the C₃₋₇-cycloalkyl group may be replaced by an imino, C₁₋₃-alkylimino, acylimino or sulphonylimino group,

[0094] A denotes a carbonylamino or aminocarbonyl group, while the hydrogen atom of the amino function may optionally be substituted by a C₁₋₃-alkyl group, and

[0095] B denotes a group of formula

[0096]  wherein

[0097] n denotes the number 1,

[0098] R⁶ denotes a hydrogen atom or a C₁₋₃-alkyl, hydroxy, amino, C₁₋₃-alkylamino group and

[0099] R⁷ denotes a hydrogen, fluorine, chlorine or bromine atom, a C₁₋₃-alkyl group wherein the hydrogen atoms may be wholly or partly replaced by fluorine atoms, a C₂₋₃-alkenyl or C₂₋₃-alkynyl, a hydroxy, C₁₋₃-alkoxy, trifluoromethoxy or cyano group,

[0100] while, unless otherwise stated, by the phrase “heteroaryl group” is meant a monocyclic 5- or 6-membered heteroaryl group optionally substituted in the carbon skeleton by a C₁₋₃-alkyl, carboxy, C₁₋₃-alkoxy-carbonyl or C₁₋₃-alkoxycarbonylamino group, while

[0101] the 6-membered heteroaryl group contains one, two or three nitrogen atoms and

[0102] the 5-membered heteroaryl group contains an imino group optionally substituted by a C₁₋₃-alkyl or phenyl-C₁₋₃-alkyl group, or an oxygen or sulphur atom or

[0103] an imino group optionally substituted by a C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl or phenyl-C₁₋₃-alkyl group, or an oxygen or sulphur atom and additionally a nitrogen atom or

[0104] an imino group optionally substituted by a C₁₋₃-alkyl or phenyl-C₁₋₃-alkyl group and two or three nitrogen atoms,

[0105] and also a phenyl ring may be fused to the above-mentioned monocyclic heteroaryl groups via two adjacent carbon atoms

[0106] and the bond is effected via a nitrogen atom or via a carbon atom of the heterocyclic moiety or a fused-on phenyl ring,

[0107] while unless otherwise stated the alkyl and alkoxy groups contained in the definitions which have more than two carbon atoms may be straight-chain or branched,

[0108] and the hydrogen atoms of the methyl or ethyl groups contained in the definitions may be wholly or partly replaced by fluorine atoms,

[0109] the tautomers, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof.

[0110] Among the embodiments referred to above, particular importance is attached to those compounds of general formula I wherein R³ denotes the hydrogen atom.

[0111] Particularly preferred compounds of general formula I are those wherein

[0112] R¹ denotes an amino, C₁₋₅-alkylamino, C₃₋₇-cycloalkylamino or (phenyl-C₁₋₃-alkyl)-amino group which may be substituted in each case at the amino nitrogen atom by a phenylcarbonyl or phenylsulphonyl group or by a C₁₋₅-alkyl or C₁₋₅-alkylcarbonyl group optionally substituted in the alkyl moiety by a carboxy group, a group which may be converted into a carboxy group in vivo, an amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or C₃₋₆-cycloalkyleneimino group, while two nitrogen atoms are separated from one another by at least two carbon atoms,

[0113] a di-(C₁₋₅-alkyl)amino or N—(C₃₋₇-cycloalkyl)-C₁₋₅-alkylamino group, while the C₁₋₅-alkyl moiety with the exception of the 1 position may be substituted in each case by a hydroxy, C₁₋₃-alkoxy, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or C₃₋₆-cycloalkyleneimino group,

[0114] a 4- to 7-membered cycloalkyleneiminocarbonyl or cycloalkyleneiminosulphonyl group, while

[0115] the cycloalkyleneimino moiety may be substituted by one or two C₁₋₃-alkyl, C₁₋₃-alkoxy-C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl, C₁₋₅-alkyloxycarbonylamino-C₁₋₃-alkyl, C₃₋₆-cycloalkylamino-C₁₋₃-alkyl, aminocarbonyl, C₁₋₃-alkylaminocarbonyl, N—(C₃₋₇-cycloalkyl)-C₁₋₅-alkylaminocarbonyl, N-(phenyl-C₁₋₃-alkyl)-C₁₋₅-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl or C₃₋₆-cycloalkyleneiminocarbonyl group or

[0116] a methylene group not adjacent to the imino group may be substituted by a hydroxy, benzyloxy, C₁₋₃-alkoxy, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or C₃₋₆-cycloalkyleneimino group and/or

[0117] a methylene group in the 3 position of a 5-membered cycloalkyleneimino group may be replaced by a sulphur atom, a sulphinyl or sulphonyl group or a methylene group in the 4 position of a 6- or 7-membered cycloalkyleneimino group may be replaced by an oxygen or sulphur atom or by an —NH—, —N—C₁₋₃-alkyl-, —N(C₂₋₃-alkanoyl)-, sulphinyl or sulphonyl group and/or

[0118] a —CH₂—CH₂— group in a 5- to 7-membered cycloalkyleneimino group may be replaced by an —NH—CO—, —CO—NH—, —CO—N(CH₃)— or a —N(CH₃)—CO—group,

[0119] a 5- to 7-membered cycloalkenyleneiminocarbonyl or cycloalkenyleneiminosulphonyl group optionally substituted by one or two C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl, C₁₋₆-cycloalkylamino-C₁₋₃-alkyl, aminocarbonyl, C₁₋₃-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl or C₃₋₆-cycloalkyleneiminocarbonyl groups, while the double bond is not bound to a nitrogen atom,

[0120] an aminocarbonyl or aminosulphonyl group optionally substituted by one or two C₁₋₅-alkyl groups,

[0121] while the substituents may be identical or different and

[0122] in each case one of the C₁₋₅-alkyl groups may be substituted by one or two C₁₋₃-alkyl, C₁₋₃-alkoxy-C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl, C₁₋₅-alkyloxycarbonylamino-C₁₋₃-alkyl, C₃₋₆-cycloalkylamino-C₁₋₃-alkyl, aminocarbonyl, C₁₋₃-alkylamino-carbonyl, N—(C₃₋₇-cycloalkyl)-C₁₋₅-alkylaminocarbonyl, N-(phenyl-C₁₋₃-alkyl)-C₁₋₅-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl or C₃₋₆-cycloalkyleneiminocarbonyl group or

[0123] a methylene group not adjacent to the imino group may be substituted by a hydroxy, benzyloxy, C₁₋₃-alkoxy, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or C₃₋₆-cycloalkyleneimino group,

[0124] a C₁₋₃-alkyl group optionally monosubstituted by an amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, hydroxy, phenyl, heteroaryl or a 4- to 7-membered cycloalkyleneimino group, while

[0125] the phenyl moiety may be substituted by a fluorine, chlorine or bromine atom, by a trifluoromethyl, C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl or C₁₋₃-alkoxy group and/or

[0126] a —CH₂—CH₂— group in a 5- to 7-membered cycloalkyleneimino group may be replaced by an —NH—CO—, —CO—NH—, —CO—N(CH₃)— or a —N(CH₃)—CO—group or

[0127] a methylene group, which is adjacent to the nitrogen atom, in a 5- to 7-membered cycloalkyleneimino group may be replaced by a carbonyl group,

[0128] or a group of formula

[0129] wherein in the heterocyclic moiety in each case a hydrogen atom may be replaced by a methylsulphonylmethyl, amino-C₁₋₃-alkyl or aminocarbonyl group and

[0130] m denotes the number 1 or 2,

[0131] R² denotes a chlorine or bromine atom, a C₁₋₃-alkyl group wherein the hydrogen atoms may be wholly or partly replaced by fluorine atoms, or a C₂₋₃-alkenyl group,

[0132] R³ denotes a hydrogen atom,

[0133] R⁴ denotes a hydrogen atom or a straight-chain or branched C₁₋₅-alkyl group which is optionally substituted by a hydroxy, C₁₋₃-alkyloxy, mercapto, C₁₋₃-alkylsulphanyl, C₁₋₃-alkylsulphinyl, C₁₋₃-alkylsulphonyl, carboxy, aminocarbonyl, C₁₋₃-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl, C₃₋₆-cycloalkyleneiminocarbonyl, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, C₃₋₆-cycloalkyleneimino, C₁₋₃-alkylcarbonylamino, C₃₋₆-cycloalkylcarbonylamino, benzyloxycarbonylamino or guanidino group,

[0134] a phenyl or heteroaryl, phenyl-C₁₋₃-alkyl or heteroaryl-C₁₋₃-alkyl group which is optionally substituted by a hydroxy, C₁₋₄-alkyloxy, benzyloxy, hydroxycarbonyl-C₁₋₃-alkoxy, C₁₋₃-alkyloxycarbonyl-C₁₋₃-alkyloxy, aminocarbonyl-C₁₋₃-alkyloxy, C₁₋₃-alkylaminocarbonyl-C₁₋₃-alkyloxy, di-(C₁₋₃-alkyl)-aminocarbonyl-C₁₋₃-alkyloxy, C₃₋₆-cycloalkyleneiminocarbonyl-C₁₋₃-alkyloxy, carboxy, C₁₋₃-alkyloxycarbonyl group,

[0135] a 4- to 7-membered cycolalkyleneimino-C₁₋₃-alkyl group or

[0136] a 4- to 7-membered cycloalkyl-C₁₋₃-alkyl group wherein one or two methylene groups may be replaced by an —NH— or —N(C₁₋₃-alkyl)- group and wherein one or two methylene groups adjacent to the —NH— or —N(C₁₋₃-alkyl)- group may each be replaced by a carbonyl group, with the proviso that a cycloalkyl group as hereinbefore defined wherein two —NH— or —N(C₁₋₃-alkyl)- groups are separated from one another by precisely one —CH₂— group are excluded,

[0137] R⁵ denotes a hydrogen atom or

[0138] R⁴ and R⁵ together with the carbon atom to which they are bound denote a C₃₋₇-cycloalkyl group, while

[0139] one of the methylene groups of the C₃₋₇-cycloalkyl group may be replaced by an imino, C₁₋₃-alkylimino, acylimino or sulphonylimino group,

[0140] A denotes a carbonylamino or aminocarbonyl group, while the hydrogen atom of the amino function may optionally be substituted by a C₁₋₃-alkyl group, and

[0141] B denotes a group of formula

[0142]  wherein

[0143] n denotes the number 1,

[0144] R⁶ denotes a hydrogen atom or a C₁₋₃-alkyl, hydroxy, amino, C₁₋₃-alkylamino group and

[0145] R⁷ denotes a fluorine, chlorine or bromine atom, a C₁₋₃-alkyl group wherein the hydrogen atoms may be wholly or partly replaced by fluorine atoms, a C₂₋₃-alkenyl, C₂₋₃-alkynyl or a hydroxy group,

[0146] while, unless otherwise stated, by the phrase “heteroaryl group” is meant a monocyclic 5- or 6-membered heteroaryl group optionally substituted in the carbon skeleton by a C₁₋₃-alkyl, carboxy, C₁₋₃-alkoxy-carbonyl or C₁₋₃-alkoxycarbonylamino group, while

[0147] the 6-membered heteroaryl group contains one, two or three nitrogen atoms and

[0148] the 5-membered heteroaryl group contains an imino group optionally substituted by a C₁₋₃-alkyl or phenyl-C₁₋₃-alkyl group, or an oxygen or sulphur atom or

[0149] an imino group optionally substituted by a C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl or phenyl-C₁₋₃-alkyl group, or an oxygen or sulphur atom and additionally a nitrogen atom or

[0150] an imino group optionally substituted by a C₁₋₃-alkyl or phenyl-C₁₋₃-alkyl group and two or three nitrogen atoms,

[0151] and also a phenyl ring may be fused to the above-mentioned monocyclic heteroaryl groups via two adjacent carbon atoms

[0152] and the bond is effected via a nitrogen atom or via a carbon atom of the heterocyclic moiety or a fused-on phenyl ring,

[0153] while unless otherwise stated the alkyl and alkoxy groups contained in the definitions which have more than two carbon atoms may be straight-chain or branched,

[0154] and the hydrogen atoms of the methyl or ethyl groups contained in the definitions may be wholly or partly replaced by fluorine atoms,

[0155] the tautomers, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof.

[0156] Most particularly preferred compounds of the above general formula I are those wherein

[0157] R¹ denotes an amino, C₁₋₅-alkylamino, C₃₋₇-cycloalkylamino or (phenyl-C₁₋₃-alkyl)-amino group which may be substituted in each case at the amino nitrogen atom by a phenylcarbonyl or phenylsulphonyl group or by a C₁₋₅-alkyl or C₁₋₅-alkylcarbonyl group optionally substituted in the alkyl moiety by a carboxy group, a group which may be converted into a carboxy group in vivo, an amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or C₃₋₆-cycloalkyleneimino group, while two nitrogen atoms are separated from one another by at least two carbon atoms,

[0158] a di-(C₁₋₅-alkyl)amino or N—(C₃₋₇-cycloalkyl)-C₁₋₅-alkylamino group, while the C₁₋₅-alkyl moiety with the exception of the 1 position may be substituted in each case by a hydroxy, C₁₋₃-alkoxy, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or C₃₋₆-cycloalkyleneimino group,

[0159] a 4- to 7-membered cycloalkyleneiminocarbonyl or cycloalkyleneiminosulphonyl group, while

[0160] the cycloalkyleneimino moiety may be substituted by one or two C₁₋₃-alkyl, C₁₋₃-alkoxy-C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl, C₁₋₅-alkyloxycarbonylamino-C₁₋₃-alkyl, C₃₋₆-cycloalkylamino-C₁₋₃-alkyl, aminocarbonyl, C₁₋₃-alkylamino-carbonyl, N—(C₃₋₇-cycloalkyl)-C₁₋₅-alkylaminocarbonyl, N-(phenyl-C₁₋₃-alkyl)-C₁₋₅-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl or C₃₋₆-cycloalkyleneiminocarbonyl group or

[0161] a methylene group not adjacent to the imino group may be substituted by a hydroxy, benzyloxy, C₁₋₃-alkoxy, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or C₃₋₆-cycloalkyleneimino group and/or

[0162] a methylene group in the 3 position of a 5-membered cycloalkyleneimino group may be replaced by a sulphur atom, a sulphinyl or sulphonyl group or

[0163] a methylene group in the 4 position of a 6- or 7-membered cycloalkyleneimino group may be replaced by an oxygen or sulphur atom or by an —NH—, —N—C₁₋₃-alkyl-, —N(C₂₋₃-alkanoyl)-, sulphinyl or sulphonyl group and/or

[0164] a —CH₂—CH₂— group in a 5- to 7-membered cycloalkyleneimino group may be replaced by an —NH—CO—, —CO—NH—, —CO—N(CH₃)— or a —N(CH₃)—CO—group,

[0165] a 5- to 7-membered cycloalkenyleneiminocarbonyl or cycloalkenyleneiminosulphonyl group optionally substituted by one or two C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl, C₁₋₆-cycloalkylamino-C₁₋₃-alkyl, aminocarbonyl, C₁₋₃-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl or C₃₋₆-cycloalkyleneiminocarbonyl groups, while the double bond is not bound to a nitrogen atom,

[0166] an aminocarbonyl or aminosulphonyl group optionally substituted by one or two C₁₋₅-alkyl groups,

[0167] while the substituents may be identical or different and

[0168] in each case one of the C₁₋₅-alkyl groups may be substituted by one or two C₁₋₃-alkyl, C₁₋₃-alkoxy-C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl, C₁₋₅-alkyloxycarbonylamino-C₁₋₃-alkyl, C₃₋₆-cycloalkylamino-C₁₋₃-alkyl, aminocarbonyl, C₁₋₃-alkylamino-carbonyl, N—(C₃₋₇-cycloalkyl)-C₁₋₅-alkylaminocarbonyl, N-(phenyl-C₁₋₃-alkyl)-C₁₋₅-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl or C₃₋₆-cycloalkyleneiminocarbonyl group or

[0169] a methylene group not adjacent to the imino group may be substituted by a hydroxy, benzyloxy, C₁₋₃-alkoxy, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or C₃₋₆-cycloalkyleneimino group,

[0170] a C₁₋₃-alkyl group optionally monosubstituted by an amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, hydroxy, phenyl, heteroaryl or a 4- to 7-membered cycloalkyleneimino group, while

[0171] the phenyl moiety may be substituted by a fluorine, chlorine or bromine atom, by a trifluoromethyl, C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₃-alkyl or C₁₋₃-alkoxy group and/or

[0172] a —CH₂—CH₂— group in a 5- to 7-membered cycloalkyleneimino group may be replaced by an —NH—CO—, —CO—NH—, —CO—N(CH₃)— or a —N(CH₃)—CO—group or

[0173] a methylene group, which is adjacent to the nitrogen atom, in a 5- to 7-membered cycloalkyleneimino group may be replaced by a carbonyl group,

[0174] or a group of formula

[0175] wherein in the heterocyclic moiety in each case a hydrogen atom may be replaced by a methylsulphonylmethyl, amino-C₁₋₃-alkyl or aminocarbonyl group and

[0176] m denotes the number 1 or 2,

[0177] R² denotes a chlorine or bromine atom, a C₁₋₃-alkyl group wherein the hydrogen atoms may be wholly or partly replaced by fluorine atoms, or a C₂₋₃-alkenyl group,

[0178] R³ denotes a hydrogen atom,

[0179] R⁴ denotes a hydrogen atom or a straight-chain or branched C₁₋₅-alkyl group which is optionally substituted by a hydroxy, C₁₋₃-alkyloxy, mercapto, C₁₋₃-alkylsulphanyl, C₁₋₃-alkylsulphinyl, C₁₋₃-alkylsulphonyl, carboxy, aminocarbonyl, C₁₋₃-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl, C₃₋₆-cycloalkyleneiminocarbonyl, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, C₃₋₆-cycloalkyleneimino, C₁₋₃-alkylcarbonylamino, C₃₋₆-cycloalkylcarbonylamino, benzyloxycarbonylamino or guanidino group,

[0180] a phenyl or heteroaryl, phenyl-C₁₋₃-alkyl or heteroaryl-C₁₋₃-alkyl group which is optionally substituted by a hydroxy, C₁₋₄-alkyloxy, benzyloxy, hydroxycarbonyl-C₁₋₃-alkoxy, C₁₋₃-alkyloxycarbonyl-C₁₋₃-alkyloxy, aminocarbonyl-C₁₋₃-alkyloxy, C₁₋₃-alkylaminocarbonyl-C₁₋₃-alkyloxy, di-(C₁₋₃-alkyl)-aminocarbonyl-C₁₋₃-alkyloxy, C₃₋₆-cycloalkyleneiminocarbonyl-C₁₋₃-alkyloxy, carboxy, C₁₋₃-alkyloxycarbonyl group,

[0181] a 4- to 7-membered cycolalkyleneimino-C₁₋₃-alkyl group or

[0182] a 4- to 7-membered cycloalkyl-C₁₋₃-alkyl group wherein one or two methylene groups may be replaced by an —NH— or —N(C₁₋₃-alkyl)- group and wherein one or two methylene groups adjacent to the —NH— or —N(C₁₋₃-alkyl)- group may each be replaced by a carbonyl group, with the proviso that a cycloalkyl group as hereinbefore defined wherein two —NH— or —N(C₁₋₃-alkyl)- groups are separated from one another by precisely one —CH₂— group are excluded,

[0183] R⁵ denotes a hydrogen atom,

[0184] A denotes a carbonylamino or aminocarbonyl group and

[0185] B denotes a group of formula

[0186]  wherein

[0187] n denotes the number 1,

[0188] R⁶ denotes a hydrogen atom or a C₁₋₃-alkyl, hydroxy, amino, C₁₋₃-alkylamino group and

[0189] R⁷ denotes a fluorine, chlorine or bromine atom, a C₁₋₃-alkyl group wherein the hydrogen atoms may be wholly or partly replaced by fluorine atoms, a C₂₋₃-alkenyl, C₂₋₃-alkynyl or a hydroxy group,

[0190] while, unless otherwise stated, by the phrase “heteroaryl group” is meant a monocyclic 5- or 6-membered heteroaryl group optionally substituted in the carbon skeleton by a C₁₋₃-alkyl, carboxy, C₁₋₃-alkoxy-carbonyl or C₁₋₃-alkoxycarbonylamino group, while

[0191] the 6-membered heteroaryl group contains one, two or three nitrogen atoms and

[0192] the 5-membered heteroaryl group contains an imino group optionally substituted by a C₁₋₃-alkyl or phenyl-C₁₋₃-alkyl group, or an oxygen or sulphur atom or

[0193] an imino group optionally substituted by a C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, C₃₋₆-cycloalkyleneimino-C₁₋₁₃-alkyl or phenyl-C₁₋₃-alkyl group, or an oxygen or sulphur atom and additionally a nitrogen atom or

[0194] an imino group optionally substituted by a C₁₋₃-alkyl or phenyl-C₁₋₃-alkyl group and two or three nitrogen atoms,

[0195] and also a phenyl ring may be fused to the above-mentioned monocyclic heteroaryl groups via two adjacent carbon atoms

[0196] and the bond is effected via a nitrogen atom or via a carbon atom of the heterocyclic moiety or a fused-on phenyl ring,

[0197] while unless otherwise stated the alkyl and alkoxy groups contained in the definitions which have more than two carbon atoms may be straight-chain or branched,

[0198] and the hydrogen atoms of the methyl or ethyl groups contained in the definitions may be wholly or partly replaced by fluorine atoms,

[0199] the tautomers, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof.

[0200] Most preferred compounds of the above general formula I are those wherein

[0201] R¹ denotes a 2,5-dihydro-1H-pyrrol-1-yl-carbonyl, pyrrolidin-1-yl-carbonyl, N-acetyl-N-cyclobutylamino, 2-(N-tert.-butoxycarbonylaminomethyl)-pyrrolidin-1-yl-carbonyl, 2-(aminomethyl)-pyrrolidin-1-yl-carbonyl, 3-oxo-piperazin-1-yl-carbonyl, 4-methyl-3-oxo-piperazin-1-yl-carbonyl, thiazolidin-3-yl-carbonyl, 1,2,3,6-tetrahydropyridin-1-yl-carbonyl, 2-methyl-thiomorpholin-4-yl-carbonyl, thiomorpholin-4-yl-carbonyl, N-isopropyl-N-methyl-aminocarbonyl, 2-methoxymethyl-pyrrolidin-1-yl-carbonyl, 3-(pyrrolidin-1-yl-methyl)-piperidin-1-yl-carbonyl, azetidin-1-yl-carbonyl, 2-methyl-pyrrolidin-1-yl-carbonyl, N-isobutyl-N-methyl-aminocarbonyl, [1,4]oxazepan-1-yl-carbonyl, 2,5-dimethyl-pyrrolidin-1-yl-carbonyl, piperidin-1-yl-carbonyl, 4-hydroxy-piperidin-1-yl-carbonyl, 4-acetyl-piperazin-1-yl-carbonyl, N,N-diethylaminocarbonyl, 3-methyl-piperidin-1-yl-carbonyl, 4-methyl-piperidin-1-yl-carbonyl, 2-aminomethyl-piperidin-1-yl-carbonyl, 3-aminomethyl-piperidin-1-yl-carbonyl, 3-(2-aminoethyl)-piperidin-1-yl-carbonyl, 3-amino-piperidin-1-yl-carbonyl or N-(2-dimethylamino)-ethyl-N-ethyl-aminocarbonyl group,

[0202] R² denotes a chlorine or bromine atom, a C₁₋₃-alkyl group wherein the hydrogen atoms may be wholly or partly replaced by fluorine atoms, or a

[0203] C₂₋₃-alkenyl group,

[0204] R³ denotes a hydrogen atom,

[0205] R⁴ denotes a hydrogen atom, the methyl, isobutyl, phenyl, benzyl, pyridine-4-yl-methyl, pyridin-2-yl-methyl, 1H-imidazol-4-yl-methyl, aminocarbonylmethyl or 4-benzyloxycarbonylaminobutyl group,

[0206] R⁵ denotes a hydrogen atom,

[0207] A denotes an aminocarbonyl or carbonylamino group and

[0208] B denotes a group of formula

[0209]  wherein

[0210] R⁶ denotes a hydrogen atom,

[0211] R⁷ denotes a fluorine, chlorine or bromine atom or a methyl group,

[0212] the tautomers, the enantiomers, the diastereomers, the mixtures thereof and the salts thereof.

[0213] For example, the following preferred compounds of general formula I may be mentioned:

[0214] (1) N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(2,5-dihydropyrrol-1-yl-carbonyl)-benzamide,

[0215] (2) N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0216] (3) N-(5-chloro-1H-benzimidazol-2-yl)methyl-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0217] (4) N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-phenyl-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0218] (5) N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-phenyl-ethyl]-3-methyl-4-(2,5-dihydropyrrol-1-yl-carbonyl)-benzamide,

[0219] (6) N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-ethynyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0220] (7) N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-ethyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0221] (8) N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(N-cyclobutyl-N-acetyl-amino)-benzamide,

[0222] (9) N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-chloro-4-[2-(N-tert.-butoxycarbonyl-aminomethyl)-pyrrolidin-1-yl-carbonyl]-benzamide,

[0223] (10) (S)-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-4-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0224] (11) (S)-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-2-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0225] (12) N-[1-(5-fluoro-1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0226] (13) N-[1-(5-cyano-1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0227] (14) N-[1-(5-methoxy-1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0228] (15) (S)-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(1H-imidazol-4-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0229] (16) (R)- and (S)4-(2-aminomethyl-pyrrolidin-1-yl-carbonyl)-3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-4-yl)-ethyl]-benzamide,

[0230] (17) N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-chloro-4-(2-aminomethyl-pyrrolidin-1-yl-carbonyl)-benzamide,

[0231] (18) 1-[N-(5-methyl-1H-benzimidazol-2-yl)]-ethyl-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0232] (19) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(3-oxo-piperazin-1-yl-carbonyl)-benzamide,

[0233] (20) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(4-methyl-3-oxo-piperazin-1-yl-carbonyl)-benzamide,

[0234] (21) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)4-(2-aminomethyl-pyrrolidin-1-yl-carbonyl)-benzamide,

[0235] (22) N-(5-chloro-1H-benzimidazol-2-yl-methyl)4-(2,3-dihydro-imidazo[2,1-b]thiazol-5-yl)-benzamide,

[0236] (23) 2-(5-chloro-1H-benzimidazol-2-yl)-N-[3-methyl-4-(pyrrolidin-1-yl-carbonyl)-phenyl]-acetamide,

[0237] (24) 3-methyl-4-(pyrrolidine-1-carbonyl)-N-[1-(5-trifluoromethyl-1H-benzimidazol-2-yl)-ethyl]-benzamide,

[0238] (25) (S)-N-[2-aminocarbonyl-1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0239] (26) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)4-(2,5-dihydropyrrol-1-yl-carbonyl)-benzamide,

[0240] (27) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(thiazolidin-3-yl-carbonyl)-benzamide (28) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)4-(1,2,3,6-tetrahydro-pyridin-1-yl-carbonyl)-benzamide,

[0241] (29) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(2-methyl-thiomorpholin-4-yl-carbonyl)-benzamide,

[0242] (30) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)4-(thiomorpholin-4-yl-carbonyl)-benzamide,

[0243] (31) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(N-isopropyl-N-methyl-aminocarbonyl)-benzamide,

[0244] (32) (R)-3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(2-methoxymethyl-pyrrolidin-1-yl-carbonyl)-benzamide,

[0245] (33) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-[3-(pyrrolidin-1-yl-methyl)-piperidin-1-yl-carbonyl]-benzamide,

[0246] (34) (S)-3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(2-methoxymethyl-pyrrolidin-1-yl-carbonyl)-benzamide,

[0247] (35) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(azetidin-1-yl-carbonyl)-benzamide,

[0248] (36) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)4-(2-methyl-pyrrolidin-1-yl-carbonyl)-benzamide,

[0249] (37) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)4-(N-isobutyl-N-methyl-aminocarbonyl)-benzamide,

[0250] (38) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-([1,4]oxazepan-1-yl-carbonyl)-benzamide,

[0251] (39) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(2,5-dimethyl-pyrrolidin-1-yl-carbonyl)-benzamide,

[0252] (40) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(piperidin-1-yl-carbonyl)-benzamide,

[0253] (41) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(4-hydroxy-piperidin-1-yl-carbonyl)-benzamide,

[0254] (42) 4-(4-acetyl-piperazin-1-yl-carbonyl)-3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-benzamide,

[0255] (43) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0256] (44) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(N,N-diethyl-aminocarbonyl)-benzamide,

[0257] (45) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(3-methyl-piperidin-1-yl-carbonyl)-benzamide,

[0258] (46) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(4-methyl-piperidin-1-yl-carbonyl)-benzamide,

[0259] (47) 4-(2-aminomethyl-piperidin-1-yl-carbonyl)-3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-benzamide,

[0260] (48) 4-(3-aminomethyl-piperidin-1-yl-carbonyl)-3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-benzamide,

[0261] (49) 4-[3-(2-amino-ethyl)-piperidin-1-yl-carbonyl]-3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-benzamide,

[0262] (50) 4-(2-aminomethyl-pyrrolidin-1-yl-carbonyl)-3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-benzamide,

[0263] (51) 4-(3-amino-piperidin-1-yl-carbonyl)-3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-benzamide,

[0264] (52) N-(6-chloro-quinolin-2-ylmethyl)-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0265] (53) N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-N-ethyl-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0266] (54) N-(6-bromo-3H-imidazo[4,5-b]pyridin-2-yl)methyl-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0267] (55) N-(6-bromo-3H-imidazo[4,5-b]pyridin-2-yl)methyl-3-methyl-4-(2,5-dihydropyrrol-1-yl-carbonyl)-benzamide,

[0268] (56) N-[1-(5-bromo-1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0269] (57) N-[(5-chloro-1H-benzimidazol-2-yl)-phenyl-methyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0270] (58) N-[1-(1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0271] (59) N-[1-(5-chloro-1H-benzimidazol-2-yl)-5-benzyloxycarbonylamino-pentyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0272] (60) N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-chloro-4-(3-oxo-piperazin-1-yl-carbonyl)-benzamide,

[0273] (61) N-[1-(5-chloro-1H-benzimidazol-2-yl)-3-methyl-butyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0274] (62) N-[1-(5-chloro-1H-benzimidazol-2-yl)]ethyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0275] (63) (S)-N-[1-(5-chloro-1H-benzimidazol-2-yl)]ethyl-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0276] (64) N-[1-(5-chloro-1H-benzimidazol-2-yl)]ethyl-3-chloro-4-[N-(2-dimethylamino)ethyl-N-ethyl-aminocarbonyl]-benzamide,

[0277] (65) N-[1-(5-chloro-1H-benzimidazol-2-yl)]ethyl-3-bromo-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0278] (66) N-[1-(5-chloro-1H-benzimidazol-2-yl)]ethyl-3-trifluoromethyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0279] (67) 4-(2-aminomethyl-pyrrolidin-1-yl-carbonyl)-N-[2-aminocarbonyl-1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-chloro-benzamide,

[0280] (68) 4-(2-aminomethyl-pyrrolidin-1-yl-carbonyl)-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(1H-imidazol-4-yl)-ethyl]-benzamide,

[0281] (69) 4-(2-aminomethyl-pyrrolidin-1-yl-carbonyl)-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-2-yl)-ethyl]-benzamide

[0282] and the salts thereof.

[0283] According to the invention, the following compounds of general formula I are of exceptional importance:

[0284] (1) N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(2,5-dihydro-pyrrol-1-yl-carbonyl)-benzamide,

[0285] (2) N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0286] (3) N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-ethyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0287] (4) (S)-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-4-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0288] (5) (S)-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(1H-imidazol-4-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0289] (6) N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-chloro-4-(2-aminomethyl-pyrrolidin-1-yl-carbonyl)-benzamide,

[0290] (7) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)4-(2-methyl-pyrrolidin-1-yl-carbonyl)-benzamide,

[0291] (8) N-[1-(5-bromo-1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0292] (9) N-[(5-chloro-1H-benzimidazol-2-yl)-phenyl-methyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0293] (10) N-[1-(5-chloro-1H-benzimidazol-2-yl)-5-benzyloxycarbonylamino-pentyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0294] (11) N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-chloro-4-(3-oxo-piperazin-1-yl-carbonyl)-benzamide,

[0295] (12) (S)-N-[1-(5-chloro-1H-benzimidazol-2-yl)]ethyl-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0296] (13) N-[1-(5-chloro-1H-benzimidazol-2-yl)]ethyl-3-bromo-4-(pyrrolidin-1-yl-carbonyl)-benzamide,

[0297] (14) N-[1-(5-chloro-1H-benzimidazol-2-yl)]ethyl-3-trifluoromethyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0298] and the salts thereof.

[0299] According to the invention the compounds of general formula I are obtained by methods known per se, for example by the following methods:

[0300] (a) In order to prepare compounds of general formula

[0301]  wherein R¹ to R⁵ are as hereinbefore defined, R¹ denotes the hydrogen atom or a C₁₋₃-alkyl group and Z¹ denotes the hydrogen atom or a protective group and B′ denotes a group of formula

[0302]  wherein R⁶ and R⁷ are as hereinbefore defined and X denotes the nitrogen atom or the CH group:

[0303] Cyclising a compound of general formula

[0304]  optionally formed in the reaction mixture, wherein

[0305] R⁴ to R⁷ are as hereinbefore defined, X denotes the nitrogen atom or the CH group, R¹ denotes the hydrogen atom or a C₁₋₃-alkyl group and Z¹ denotes the hydrogen atom or a protective group, then cleaving any protective group which may be present.

[0306] The cyclisation is conveniently carried out in a solvent or mixture of solvents such as ethanol, isopropanol, glacial acetic acid, benzene, chlorobenzene, toluene, xylene, glycol, glycolmonomethylether, diethyleneglycoldimethylether, sulpholane, dimethylformamide or tetraline, dimethylsulphoxide, methylene chloride, chloroform, tetrachloromethane, for example at temperatures between 0 and 250° C., but preferably between 20 and 100° C., optionally in the presence of a condensing agent such as phosphorus oxychloride, thionyl chloride, sulphurylchloride, sulphuric acid, p-toluenesulphonic acid, methanesulphonic acid, hydrochloric acid, phosphoric acid, polyphosphoric acid, acetic acid, acetic anhydride, N,N-dicyclohexylcarbodiimide or optionally also in the presence of a base such as potassium ethoxide or potassium-tert.-butoxide. The cyclisation may, however, also be carried out with a solvent and/or condensing agent.

[0307] (b) In order to prepare a compound of general formula

[0308]  wherein B and R¹ to R⁵ are defined as in claim 1 and R¹ denotes the hydrogen atom or a C₁₋₃-alkyl group:

[0309] acylation of a compound of general formula

[0310]  wherein B, R⁴ and R⁵ are as hereinbefore defined, R¹ denotes the hydrogen atom or a C₁₋₃-alkyl group and Z¹ represents the hydrogen atom,

[0311] with a carboxylic acid or a reactive carboxylic acid derivative of general formula

[0312]  wherein R¹ to R³ are as hereinbefore defined and X denotes a hydroxy, C₁₋₄-alkoxy group, a halogen atom or an anhydride.

[0313] The acylation is conveniently carried out with a corresponding halide or anhydride in a solvent such as methylene chloride, chloroform, carbon tetrachloride, ether, tetrahydrofuran, dioxane, benzene, toluene, acetonitrile, dimethylformamide, sodium hydroxide solution or sulpholane optionally in the presence of an inorganic or organic base at temperatures between −20 and 200° C., but preferably at temperatures between −10 and 160° C. The acylation may however also be carried out with the free acid optionally in the presence of an acid-activating agent or a dehydrating agent, e.g. in the presence of isobutyl chloroformate, thionyl chloride, trimethylchlorosilane, hydrogen chloride, sulphuric acid, methanesulphonic acid, p-toluenesulphonic acid, phosphorus trichloride, phosphorus pentoxide, N,N′-dicyclohexylcarbodiimide, N,N′-dicyclohexylcarbodiimide/N-hydroxysuccinimide or 1-hydroxy-benzotriazole, N,N′-carbonyldiimidazole, O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyl-uronium tetrafluoroborate/N-methylmorpholine, O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate/N-ethyldiisopropylamine, N,N′-thionyldiimidazole or triphenylphosphine/carbon tetrachloride, at temperatures between −20 and 200° C., but preferably at temperatures between −10 and 160° C.

[0314] (c) In order to prepare a compound of general formula

[0315]  wherein B and R¹ to R⁵ are as hereinbefore defined and R¹ denotes the hydrogen atom or a C₁₋₃-alkyl group:

[0316] acylating a compound of general formula

[0317]  wherein R¹ to R³ are as hereinbefore defined and R¹ denotes the hydrogen atom or a C₁₋₃-alkyl group,

[0318] with a carboxylic acid or a reactive carboxylic acid derivative of general formula

[0319]  wherein B, R⁴ and R⁵ are as hereinbefore defined and X denotes a hydroxy, C₁₋₄-alkoxy group or a halogen atom.

[0320] The acylation is conveniently carried out with a corresponding halide or anhydride in a solvent such as methylene chloride, chloroform, carbon tetrachloride, ether, tetrahydrofuran, dioxane, benzene, toluene, acetonitrile, dimethylformamide or sulpholane optionally in the presence of an inorganic or organic base at temperatures between −20 and 200° C., but preferably at temperatures between −10 and 160° C.

[0321] The acylation may however also be carried out with the free acid or an ester optionally in the presence of an acid-activating agent or a dehydrating agent, e.g. in the presence of isobutyl chloroformate, thionyl chloride, trimethylchlorosilane, hydrogen chloride, sulphuric acid, methanesulphonic acid, p-toluenesulphonic acid, phosphorus trichloride, phosphorus pentoxide, triethylamine, N,N′-dicyclohexylcarbodiimide, N,N′-dicyclohexylcarbodiimide/N-hydroxysuccinimide or 1-hydroxy-benzotriazole, O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyl-uronium tetrafluoroborate/N-methylmorpholine, propanephosphonic acid-cyclo-anhydride/N-methylmorpholine, N,N′-carbonyldiimidazole or N,N′-thionyldiimidazole or triphenylphosphine/carbon tetrachloride, at temperatures between −20 and 200° C., but preferably at temperatures between −10 and 160° C.

[0322] Other methods of amide coupling are described for example in P. D. Bailey, I. D. Collier, K. M. Morgan in “Comprehensive Functional Group Interconversions”, Vol. 5, page 257ff., Pergamon 1995.

[0323] In the reactions described above any reactive groups present such as hydroxy, carboxy, amino, alkylamino or imino groups may be protected during the reaction by conventional protective groups which are cleaved again after the reaction.

[0324] For example a suitable protective group for a hydroxy group is the methoxy, benzyloxy, trimethylsilyl, acetyl, benzoyl, tert.-butyl, trityl, benzyl or tetrahydro-pyranyl group,

[0325] a suitable protective group for a carboxyl group is the trimethylsilyl, methyl, ethyl, tert.-butyl, benzyl or tetrahydropyranyl group and

[0326] a suitable protective group for an amino, alkylamino or imino group is the acetyl, trifluoroacetyl, benzoyl, ethoxycarbonyl, tert.-butoxycarbonyl, benzyloxycarbonyl, benzyl, methoxybenzyl or 2,4-dimethoxybenzyl group and additionally a suitable protective group for the amino group is the phthalyl group.

[0327] Other protective groups and their cleaving are described in T. W. Greene, P. G. M. Wuts, “Protective Groups in Organic Synthesis”, Wiley, 1991.

[0328] Any protective group used is optionally subsequently cleaved for example by hydrolysis in an aqueous solvent, e.g. in water, isopropanol/water, tetrahydrofuran/water or dioxane/water, in the presence of an acid such as trifluoroacetic acid, hydrochloric acid or sulphuric acid or in the presence of an alkali metal base such as lithium hydroxide, sodium hydroxide or potassium hydroxide or by means of ether splitting, e.g. in the presence of iodotrimethylsilane, at temperatures between 0 and 100° C., preferably at temperatures between 10 and 50° C.

[0329] A benzyl, methoxybenzyl or benzyloxycarbonyl group, however, is cleaved by hydrogenolysis, for example, e.g. with hydrogen in the presence of a catalyst such as palladium/charcoal in a solvent such as methanol, ethanol, ethyl acetate, dimethylformamide, dimethylformamide/acetone or glacial acetic acid, optionally with the addition of an acid such as hydrochloric acid at temperatures between 0 and 50° C., but preferably at ambient temperature, and under a hydrogen pressure of 1 to 7 bar, but preferably 1 to 5 bar.

[0330] A methoxybenzyl group may also be cleaved in the presence of an oxidising agent such as cerium(IV)ammonium nitrate in a solvent such as methylene chloride, acetonitrile or acetonitrile/water at temperatures between 0 and 50° C., but preferably at ambient temperature.

[0331] A methoxy group is conveniently cleaved in the presence of boron tribromide in a solvent such as methylene chloride at temperatures between −35 and −25° C.

[0332] A 2,4-dimethoxybenzyl group, however, is preferably cleaved in trifluoroacetic acid in the presence of anisol.

[0333] A tert.-butyl or tert.-butyloxycarbonyl group is preferably cleaved by treatment with an acid such as trifluoroacetic acid or hydrochloric acid, optionally using a solvent such as methylene chloride, dioxane or ether.

[0334] A phthalyl group is preferably cleaved in the presence of hydrazine or a primary amine such as methylamine, ethylamine or n-butylamine in a solvent such as methanol, ethanol, isopropanol, toluene/water or dioxane at temperatures between 20 and 50° C.

[0335] An allyloxycarbonyl group is cleaved by treatment with a catalytic amount of tetrakis-(triphenylphosphine)-palladium(0), preferably in a solvent such as tetrahydrofuran and preferably in the presence of an excess of a base such as morpholine or 1,3-dimedone at temperatures between 0 and 100° C., preferably at ambient temperature and under inert gas, or by treatment with a catalytic amount of tris-(triphenylphosphine)-rhodium(I)chloride in a solvent such as aqueous ethanol and optionally in the presence of a base such as 1,4-diazabicyclo[2.2.2]octane at temperatures between 20 and 70° C.

[0336] The compounds of general formulae III to VIII used as starting materials, some of which are known from the literature, may be obtained by methods known from the literature. Their preparation is also described in the Examples.

[0337] The compounds of general formulae III and V may for example be prepared analogously to K. Maekawa, J. Ohtani, Agr. Biol. Chem. 1976, 40, 791-799.

[0338] Thus for example a compound of general formula IV is obtained by acylation of a corresponding o-diamino compound with a corresponding reactive acyl derivative.

[0339] The preparation of carboxylic acid derivatives of general formulae VI and VIII is described in “Methoden der organischen Chemie” (Houben-Weyl), volume E5, Carboxylic acids and carboxylic acid derivatives, 4th edition, published by Thieme, Stuttgart 1985.

[0340] Moreover, the compounds of general formula I obtained may be resolved into their enantiomers and/or diastereomers.

[0341] Thus, for example, the compounds of general formula I obtained which occur as racemates may be separated by methods known per se (cf. Allinger N. L. and Eliel E. L. in “Topics in Stereochemistry”, Vol. 6, Wiley Interscience, 1971) into their optical enantiomers and compounds of general formula I with at least 2 asymmetric carbon atoms may be resolved into their diastereomers on the basis of their physical-chemical differences using methods known per se, e.g. by chromatography and/or fractional crystallisation, and, if these compounds are obtained in racemic form, they may subsequently be resolved into the enantiomers as mentioned above.

[0342] The enantiomers are preferably separated by column separation on chiral phases or by recrystallisation from an optically active solvent or by reacting with an optically active substance which forms salts or derivatives such as e.g. esters or amides with the racemic compound, particularly acids and the activated derivatives or alcohols thereof, and separating the diastereomeric mixture of salts or derivatives thus obtained, e.g. on the basis of their differences in solubility, whilst the free antipodes may be released from the pure diastereomeric salts or derivatives by the action of suitable agents. Optically active acids in common use are e.g. the D- and L-forms of tartaric acid or dibenzoyltartaric acid, di-o-tolyltartaric acid, malic acid, mandelic acid, camphorsulphonic acid, glutamic acid, aspartic acid or quinic acid. An optically active alcohol may be, for example, (+) or (−)-menthol and an optically active acyl group in amides, for example, may be a (+)- or (−)-menthyloxycarbonyl.

[0343] Furthermore, the compounds of formula I may be converted into the salts thereof, particularly for pharmaceutical use into the physiologically acceptable salts with inorganic or organic acids. Acids which may be used for this purpose include for example hydrochloric acid, hydrobromic acid, sulphuric acid, methanesulphonic acid, phosphoric acid, fumaric acid, succinic acid, lactic acid, citric acid, tartaric acid or maleic acid.

[0344] Moreover, if the new compounds of formula I contain a carboxy group, they may subsequently, if desired, be converted into the salts thereof with inorganic or organic bases, particularly for pharmaceutical use into the physiologically acceptable salts thereof. Suitable bases for this purpose include for example sodium hydroxide, potassium hydroxide, cyclohexylamine, ethanolamine, diethanolamine and triethanolamine.

[0345] As already mentioned, the compounds of general formula I and the tautomers, enantiomers, diastereomers and physiologically acceptable salts thereof have valuable pharmacological properties, particularly an antithrombotic activity which is preferably based on an effect on thrombin or factor Xa, for example on a thrombin-inhibiting or factor Xa-inhibiting activity, on a prolonging effect on the aPTT time and on an inhibitory effect on related serine proteases such as e.g. urokinase, factor VIIa, factor IX, factor XI and factor XII.

[0346] The compounds listed in the Experimental Section were investigated for their effect on the inhibition of factor Xa as follows:

[0347] Method:

[0348] Enzyme-kinetic measurement with chromogenic substrate. The quantity of p-nitroaniline (pNA) released from the colourless chromogenic substrate by human factor Xa is determined photometrically at 405 nm. It is proportional to the activity of the enzyme used. The inhibition of the enzyme activity by the test substance (in relation to the solvent control) is determined at various concentrations of test substance and from this the IC₅₀ is calculated, as the concentration which inhibits the factor Xa used by 50%.

[0349] Material:

[0350] Tris(hydroxymethyl)-aminomethane buffer (100 mMol) and sodium chloride (150 mMol), pH 8.0 plus 1 mg/ml Human Albumin Fraction V, protease-free

[0351] Factor Xa (Calbiochem), spec. activity: 217 lU/mg, final concentration: 7 lU/ml for each reaction mixture

[0352] Substrate S 2765 (Chromogenix), final concentration: 0.3 mM/I (1 KM) for each reaction mixture

[0353] Test substance: final concentration 100, 30, 10, 3, 1, 0.3, 0.1, 0.03, 0.01, 0.003, 0.001 μMol/l

[0354] Procedure:

[0355] 10 μl of a 23.5-times concentrated starting solution of the test substance or solvent (control), 175 μl of TRIS/HSA buffer and 25 μl of a 65.8 U/L Factor Xa working solution are incubated for 10 minutes at 37° C. After the addition of 25 μi of S 2765 working solution (2.82 mMol/l) the sample is measured in a photometer (SpectraMax 250) at 405 nm for 600 seconds at 37° C.

[0356] Evaluation:

[0357] 1. Determining the maximum increase (deltaOD/minutes) over 21 measuring points.

[0358] 2. Determining the % inhibition based on the solvent control.

[0359] 3. Plotting a dosage/activity curve (% inhibition vs substance concentration).

[0360] 4. Determining the IC₅₀ by interpolating the X-value (substance concentration) of the dosage/activity curve at Y=50% inhibition.

[0361] All the compounds tested had an IC₅₀ value of less than 100 μmol/L.

[0362] The compounds prepared according to the invention are generally well tolerated.

[0363] In view of their pharmacological properties the new compounds and the physiologically acceptable salts thereof are suitable for the prevention and treatment of venous and arterial thrombotic diseases, such as for example the prevention and treatment of deep leg vein thrombosis, for preventing reocclusions after bypass operations or angioplasty (PT(C)A), and occlusion in peripheral arterial diseases, and for preventing and treating pulmonary embolism, disseminated intravascular coagulation, for preventing and treating coronary thrombosis, for preventing stroke and the occlusion of shunts. In addition, the compounds according to the invention are suitable for antithrombotic support in thrombolytic treatment, such as for example with alteplase, reteplase, tenecteplase, staphylokinase or streptokinase, for preventing long-term restenosis after PT(C)A, for the prevention and treatment of ischaemic incidents in patients with all forms of coronary heart disease, for preventing metastasis and the growth of tumours and inflammatory processes, e.g. in the treatment of pulmonary fibrosis, for preventing and treating rheumatoid arthritis, for preventing and treating fibrin-dependent tissue adhesions and/or the formation of scar tissue and for promoting wound healing processes. The new compounds and the physiologically acceptable salts thereof may be used therapeutically in conjunction with acetylsalicylic acid, with inhibitors of platelet aggregation such as fibrinogen receptor antagonists (e.g. abciximab, eptifibatide, tirofiban, roxifiban), with physiological activators and inhibitors of the clotting system and the recombinant analogues thereof (e.g. Protein C, TFPI, antithrombin), with inhibitors of ADP-induced aggregation (e.g. clopidogrel, ticlopidine), with P₂T receptor antagonists (e.g. cangrelor) or with combined thromboxane receptor antagonists/synthetase inhibitors (e.g. terbogrel).

[0364] The dosage required to achieve such an effect is appropriately 0.01 to 3 mg/kg, preferably 0.03 to 1.0 mg/kg by intravenous route, and 0.03 to 30 mg/kg, preferably 0.1 to 10 mg/kg by oral route, in each case administered 1 to 4 times a day.

[0365] For this purpose, the compounds of formula I prepared according to the invention may be formulated, optionally together with other active substances, with one or more inert conventional carriers and/or diluents, e.g. with corn starch, lactose, glucose, microcrystalline cellulose, magnesium stearate, polyvinylpyrrolidone, citric acid, tartaric acid, water, water/ethanol, water/glycerol, water/sorbitol, water/polyethylene glycol, propylene glycol, cetylstearyl alcohol, carboxymethylcellulose or fatty substances such as hard fat or suitable mixtures thereof, to produce conventional galenic preparations such as plain or coated tablets, capsules, powders, suspensions or suppositories.

[0366] The Examples which follow are intended to illustrate the invention without restricting its scope:

EXPERIMENTAL SECTION

[0367] As a rule, melting points, IR, UV, ¹H-NMR and/or mass spectra have been obtained for the compounds prepared. Unless otherwise stated, R_(f) values were determined using ready-made silica gel 60 F₂54 TLC plates (E. Merck, Darmstadt, Item no. 1.05714) without chamber saturation. The R_(f) values given under the heading Alox were determined using ready-made aluminium oxide 60 F₂₅₄ TLC plates (E. Merck, Darmstadt, Item no. 1.05713) without chamber saturation. The R_(f) values given under the heading Reversed-phase-8 were determined using ready-made RP-8 F₂54s TLC plates (E. Merck, Darmstadt, Item no. 1.15684) without chamber saturation. The ratios given for the eluants refer to units by volume of the solvents in question. For chromato-graphic purification silica gel made by Messrs Millipore (MATREX™, 35-70 my) was used. Unless more detailed information is provided as to the configuration, it is not clear whether the products are pure stereoisomers or mixtures of enantiomers and diastereomers.

[0368] The following abbreviations are used in the descriptions of the experiments:

[0369] Boc tert.-butoxycarbonyl

[0370] DMSO dimethylsulphoxide

[0371] DMF dimethylformamide

[0372] o ortho

[0373] rac. racemic

[0374] TBTU: O-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyl-uronium

[0375] tetrafluoroborate

[0376] tert.-tertiary

[0377] The HPLC/MS data were produced using the following system:

[0378] Waters ZMD, Alliance 2690 HPLC, Waters 2700 Autosampler, Waters 996 diode array detector

[0379] The following was used as the mobile phase:

[0380] A: water with 0.1% trifluoroacetic acid

[0381] B: acetonitrile with 0.1% trifluoroacetic acid time in min % A % B flow rate in ml/min 0.0 95 5 1.00 0.1 95 5 1.00 5.1 2 98 1.00 6.5 2 98 1.00 7.0 95 5 1.00

[0382] The stationary phase used was a Waters column X-Terra™ MS C₁₈ 3.5 μm, 4.6 mm×50 mm (column temperature: constant at 25° C.)

[0383] The diode array detection took place in a wavelength range from 210-500 nm Range of mass-spectrometric detection: m/z 120 to m/z 950

EXAMPLE 1

[0384] rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(2,5-dihydro-pyrrol-1-yl-carbonyl)-benzamide

[0385] (a) rac.-N′-benzyloxycarbonyl-N-(2-amino-4-chloro)phenyl-alaninamide and rac.-N′-benzyloxycarbonyl-N-(2-amino-5-chloro)phenyl-alaninamide

[0386] 4.50 g (20.2 mmol) rac.-N-benzyloxycarbonylalanine and 3.60 g (22.2 mmol) N,N′-carbonyldiimidazole are stirred in 25 ml of dimethylformamide for 10 minutes and then slowly combined with a solution of 4-chloro-o-phenylenediamine (6.00 g, 42.1 mmol) and 4.88 ml (44.4 mmol) N-methylmorpholine in 25 ml of dimethylformamide and stirred for 16 hours at ambient temperature. Then water is added and the mixture is extracted three times with methylene chloride. The combined organic phases are dried with sodium sulphate and evaporated down. The residue is purified by chromatography with silica gel (gradient: methylene chloride/ethanol=100:0->95:5). The title compounds were obtained as a 4:1 mixture with diacylated phenylenediamine.

[0387] Yield: 6.00 g (mixture)

[0388] R_(f) value: 0.35 (silica gel; dichloromethane/ethanol=19:1)

[0389] (b) rac.-N-benzyloxycarbonyl-1-(5-chloro-1H-benzimidazol-2-yl)ethylamine

[0390] The mixture prepared in Example 1a (6.00 g) is dissolved in 30 ml glacial acetic acid, heated to boiling for 8 hours and stirred for a further 16 hours at ambient temperature. The acetic acid is distilled off and the crude product purified by chromatography with silica gel (gradient: methylene chloride/ethanol=100:0->98:2).

[0391] Yield: 5.00 g (contaminated, approx. 80% title compound)

[0392] R_(f) value: 0.40 (silica gel; dichloromethane/ethanol=19:1)

[0393] (c) rac-1-(5-chloro-benzimidazol-2-yl)ethylamine

[0394] 5.00 g (contaminated) rac.-N-benzyloxycarbonyl-1-(5-chloro-1H-benzimidazol-2-yl)ethylamine are dissolved in a mixture of 100 ml of methanol and 40 ml methylene chloride, combined with 1.0 g palladium on charcoal and hydrogenated for 1 hour at 3.4 bar hydrogen pressure. The solvents are distilled off and the crude product is purified by chromatography with silica gel (eluant: methylene chloride/ethanol=95:5+0.2% ammonia).

[0395] Yield: 1.08 g (25% over 3 steps)

[0396] R_(f) value: 0.37 (silica gel; dichloromethane/ethanol=4:1+2% ammonia)

[0397] C₉H₁₀ClN₃ (195.65)

[0398] Mass spectrum: (M+H)⁺=196/198 (chlorine isotope)

[0399] (d) 4-(2,5-dihydro-pyrrol-1-yl-carbonyl)-3-methyl-bromobenzene

[0400] 25.0 g (0.12 mol) of 4-bromo-2-methylbenzoic acid are dissolved in 250 ml of dimethylformamide and after the addition of 41.7 g (0.13 mol) of 0-(benzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate (TBTU), 14.3 ml (0.13 mol) of N-methylmorpholine and 9.6 ml (0.12 mol) of 2,5-dihydropyrrole the mixture is stirred for 16 hours at ambient temperature. Then it is poured onto ice water and extracted with ethyl acetate. The combined organic extracts are washed with sodium hydrogen carbonate solution, dried over sodium sulphate and concentrated by evaporation.

[0401] Yield: 31.6 g (97% of theory)

[0402] R_(f) value: 0.45 (silica gel; dichloromethane/ethanol=19:1)

[0403] (e) 4-(2,5-dihydropyrrol-1-yl-carbonyl)-3-methyl-benzonitrile

[0404] 31.6 g (0.11 mol) of 4-(2,5-dihydropyrrol-1-yl-carbonyl)-3-methyl-bromobenzene are dissolved in 125 ml of dimethylformamide, and combined with 20.2 g (0.23 mol) of copper cyanide and 3.2 g (2.7 mmol) of tetrakis-triphenylphosphine-palladium-(0). The suspension is stirred for 20 hours at 140° C. Then it is cooled to 80° C., combined with 150 ml of water, 150 ml of ethyl acetate and 25 g Celite and filtered through Celite. The organic phase is separated off, washed with sodium chloride solution, dried over sodium sulphate and concentrated by evaporation. The residue is chromatographed on silica gel, eluting with ethyl acetate/ethanol (50:1 and 19:1). The corresponding fractions are combined and concentrated by evaporation.

[0405] Yield: 11.7 g (49% of theory)

[0406] R_(f) value: 0.55 (silica gel; ethyl acetate/ethanol=9:1)

[0407] (f) 4-(2,5-dihydropyrrol-1-yl-carbonyl)-3-methyl-benzoic acid

[0408] 10.6 g (0.05 mol) of 4-(2,5-dihydropyrrol-1-yl-carbonyl)-3-methyl-benzonitrile are stirred in 106 ml of ethanol and 106 ml of 10 molar sodium hydroxide solution for 30 minutes at 80° C. Then the ethanol is distilled off, the residue is dissolved in water, filtered through activated charcoal and acidified with 6 molar hydrochloric acid. The acid precipitated is suction filtered and dried at 40° C.

[0409] Yield: 7.5 g (64% of theory)

[0410] R_(f) value: 0.29 (silica gel; dichloromethane/ethanol=9:1)

[0411] (g) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(2,5-dihydropyrrol-1-yl-carbonyl)-benzamide

[0412] A solution of 0.201 g (0.869 mmol) 3-methyl-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzoic acid, 0.335 g (1.04 mmol) TBTU and 0.33 ml (1.9 mmol) diisopropylethylamine in 15 ml of tetrahydrofuran is stirred for 10 minutes at ambient temperature and then 0.170 g (0.869 mmol) rac-1-(5-chloro-1H-benzimidazol-2-yl)ethylamine are added. The mixture is stirred for 16 hours at ambient temperature, combined with water and extracted three times with ethyl acetate. The combined organic phases are washed once with 2M NaOH and three times with water, dried with sodium sulphate and concentrated.

[0413] Yield: 0.34 g (96% of theory)

[0414] R_(f) value: 0.50 (silica gel; dichloromethane/ethanol=9:1)

[0415] C₂₂H₂₁ClN₄O₂ (408.89)

[0416] Mass spectrum: (M−H)⁻=407/409 (chlorine isotope) (M+H)⁺=409/411 (chlorine isotope)

EXAMPLE 2

[0417] rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0418] Prepared analogously to Example 1g from 3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzoic acid, TBTU, diisopropylethylamine and rac-1-(5-chloro-1H-benzimidazol-2-yl)ethylamine in tetrahydrofuran.

[0419] Yield: quantitative

[0420] R_(f) value: 0.50 (silica gel; dichloromethane/ethanol=9:1)

[0421] C₂₂H₂₃ClN₄O₂ (410.91)

[0422] Mass spectrum: (M−H)⁻=409/411 (chlorine isotope)

EXAMPLE 3

[0423] N-(5-chloro-1H-benzimidazol-2-yl)methyl-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0424] (a) N′-tertbutoxycarbonyl-N-(2-amino-4-chlorphenyl)-glycinamide and regioisomer

[0425] Prepared analogously to Example 1a from N-tertbutoxycarbonyl-glycine, N,N′-carbonyldiimidazole, 4-chloro-o-phenylenediamine and N-methylmorpholine in dimethylformamide and subsequent purification by chromatography on silica gel (gradient: methylene chloride/ethanol=100:0->88:12).

[0426] Yield: 40% (mixture)

[0427] R_(f) value: 0.24 (silica gel; dichloromethane/ethanol=95:5)

[0428] (b) N-tertbutoxycarbonyl-C-(5-chloro-1H-benzimidazol-2-yl)methylamine

[0429] Prepared analogously to Example 1 b from N′-tertbutoxycarbonyl-N-(2-amino-4-chloro)phenyl-glycinamide in glacial acetic acid and subsequent purification by chromatography on silica gel (gradient: methylene chloride/ethanol=100:0->94:6).

[0430] Yield: 23%

[0431] R_(f) value: 0.45 (silica gel; petroleum ether/ethyl acetate=8:2)

[0432] C₁₃H₁₆ClN₃O₂ (281.74)

[0433] Mass spectrum: (M+H)⁺=282/284 (chlorine isotope)

[0434] (c) C-(5-chloro-1H-benzimidazol-2-yl)methylamine

[0435] 4.62 g (16.398 mmol) NM-tertbutoxycarbonyl-C-(5-chloro-1H-benzimidazol-2-yl)methylamine are dissolved in 100 ml saturated ethanolic hydrogen chloride solution and stirred for 2 hours at ambient temperature. Then all the volatile constituents are removed under reduced pressure and the crude product is further reacted.

[0436] Yield: quantitative

[0437] R_(f) value: 0.35 (silica gel; petroleum ether/ethyl acetate=8:2)

[0438] (d) N-(5-chloro-1H-benzimidazol-2-yl)methyl-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0439] Prepared analogously to Example 1g from 3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzoic acid, TBTU, diisopropylethylamine and C-(5-chloro-1H-benzimidazol-2-yl)methylamine in tetrahydrofuran.

[0440] Yield: 99% (over 2 steps)

[0441] R_(f) value: 0.77 (silica gel; dichloromethane/ethanol=4:1)

[0442] C₂₁H₂₁ClN₄O₂ (396.88)

[0443] Mass spectrum: (M+H)⁺=397/399 (chlorine isotope)

EXAMPLE 4

[0444] rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-phenyl-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0445] (a) rac.-N′-tertbutoxycarbonyl-N-(2-amino-4-chlorophenyl)-phenylalanin-amide and Regioisomer

[0446] Prepared analogously to Example 1a from rac.-N-tertbutoxycarbonyl-phenylalanine, N,N′-carbonyldiimidazole, 4-chloro-o-phenylenediamine and N-methylmorpholine in dimethylformamide and subsequent purification by chromatography on silica gel (gradient: methylene chloride/ethanol=100:0->98:2).

[0447] Yield: 50%

[0448] R_(f) value: 0.67 (silica gel; dichloromethane/ethanol=9:1)

[0449] C₂₀H₂₄ClN₃O₃ (389.89)

[0450] Mass spectrum: (M−H)⁻=388/390 (chlorine isotope)

[0451] (b) rac.-N-acetyl-1-(5-chloro-benzimidazol-2-yl)-2-phenyl-ethylamine

[0452] Prepared analogously to Example 1 b from rac.-N′-tertbutoxycarbonyl-N-(2-amino-4-chlorophenyl)-phenylalanine-amide and its regioisomer in glacial acetic acid and subsequent purification by chromatography on silica gel (gradient: methylene chloride/ethanol=99:1->97:3).

[0453] Yield: 50%

[0454] R_(f) value: 0.30 (silica gel; dichloromethane/ethanol=19:1)

[0455] C₁₇H₁₆ClN₃O (313.79)

[0456] Mass spectrum: (M+H)⁺=314/316 (chlorine isotope)

[0457] (c) rac-1-(5-chloro-benzimidazol-2-yl)-2-phenyl-ethylamine

[0458] 1.35 g (4.302 mmol) rac.-N-acetyl-1-(5-chloro-benzimidazol-2-yl)-2-phenyl-ethylamine are placed in a mixture of 20 ml 4-molar hydrochloric acid and 15 ml of methanol and the mixture is refluxed for 2 hours. Then all the volatile constituents are removed under reduced pressure. The crude product is further reacted directly.

[0459] R_(f) value: 0.50 (silica gel; dichloromethane/ethanol=8:2)

[0460] (d) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-phenyl-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0461] Prepared analogously to Example 1g from 3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzoic acid, TBTU, diisopropylethylamine and rac-1-(5-chloro-benzimidazol-2-yl)-2-phenyl-ethylamine in tetrahydrofuran.

[0462] Yield: 85% (over 2 steps)

[0463] R_(f) value: 0.52 (silica gel; dichloromethane/ethanol=9:1)

[0464] C₂₈H₂₇ClN₄O₂ (487.01)

[0465] Mass spectrum: (M−H)⁻=485/487 (chlorine isotope)

EXAMPLE 5

[0466] rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-phenyl-ethyl]-3-methyl-4-(2,5-dihydropyrrol-1-yl-carbonyl)-benzamide

[0467] Prepared analogously to Example 1g from 3-methyl-4-(2,5-dihydropyrrol-1-yl-carbonyl)benzoic acid, TBTU, diisopropylethylamine and rac-1-(5-chloro-benzimidazol-2-yl)-2-phenyl-ethylamine in tetrahydrofuran.

[0468] Yield: 90%

[0469] R_(f) value: 0.52 (silica gel; dichloromethane/ethanol=9:1)

[0470] C₂₈H₂₅ClN₄O₂ (484.99)

[0471] Mass spectrum: (M+H)⁺=485/487 (chlorine isotope)

EXAMPLE 6

[0472] rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-ethynyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0473] (a) 3-bromo-4-(pyrrolidin-1-yl-carbonyl)-benzoic acid

[0474] 100 g (0.388 mol) 2-bromoterephthalic acid are dissolved in 700 ml N,N-dimethylformamide and slowly combined with 69.2 g (0.427 mol) N,N′-carbonyldiimidazole with stirring. After total dissolution the mixture is stirred for 15 minutes at ambient temperature and then 48.5 ml (0.582 mol) pyrrolidine and 93.9 ml (0.854 mol) N-methylmorpholine are slowly added dropwise one after the other. The mixture is stirred for 2.5 days at ambient temperature and then concentrated in vacuo. The residue is combined with distilled water and acidified with 2-molar hydrochloric acid solution. The aqueous phase is extracted with ethyl acetate. The precipitate formed is suction filtered and dried at 40° C.

[0475] Yield: 29.4 g (25%)

[0476] R_(f) value: 0.30 (silica gel; dichloromethane/ethanol=9:1)

[0477] C₁₂H₁₂BrNO₃ (298.14)

[0478] Mass spectrum: (M+H)⁺=298/300 (bromine isotope)

[0479] (b) methyl 3-bromo-4-(pyrrolidin-1-yl-carbonyl)-benzoate

[0480] 20 g (67.1 mmol) 3-bromo-4-(pyrrolidin-1-yl-carbonyl)-benzoic acid are dissolved in 400 ml N,N-dimethylformamide and combined with 21.9 g (67.1 mmol) caesium carbonate with stirring. Then 4.21 ml (67.1 mmol) iodomethane are slowly added dropwise at ambient temperature and the mixture is stirred for 16 hours at ambient temperature. After the solid constituents have been removed by filtration with suction volatile constituents are removed in vacuo.

[0481] Yield: 20.94 g (75%)

[0482] R_(f) value: 0.42 (silica gel; dichloromethane/ethanol=98:2)

[0483] C₁₃H₁₄BrNO₃ (312.17)

[0484] Mass spectrum: (M+H)⁺=312/314 (bromine isotope)

[0485] (c) methyl 4-(pyrrolidin-1-yl-carbonyl)-3-(2-trimethylsilyl-ethynyl)-benzoate

[0486] 18 g (57.7 mmol) methyl 3-bromo-4-(pyrrolidin-1-yl-carbonyl)-benzoate are placed under a nitrogen atmosphere together with 6.66 g (5.77 mmol) tetrakis-triphenylphosphine-palladium(0) and 0.439 g (2.31 mmol) copper(I)iodide in 150 ml N,N-diisopropylamine, the mixture is heated to 80° C. and 16.6 ml (115 mmol) trimethylsilyl-ethyne are added. The reaction mixture is stirred for 8 hours at 80° C. and then for 16 hours at ambient temperature. Then volatile constituents are eliminated in vacuo, the residue is taken up in ethyl acetate, insoluble matter is filtered off and the solvent is eliminated in vacuo. The residue is purified by chromatography on silica gel (gradient: dichloromethane/ethanol=100:0->95:5).

[0487] Yield: 7.7 g (41%).

[0488] R_(f) value: 0.44 (silica gel; dichloromethane/ethanol=95:5)

[0489] C₁₈H₂₃NO₃Si (329.48)

[0490] Mass spectrum: (M+H)⁺=330

[0491] (d) 3-ethynyl-4-(pyrrolidin-1-yl-carbonyl)-benzoic acid

[0492] 7.70 g (23.4 mmol) methyl 4-(pyrrolidin-1-yl-carbonyl)-3-(2-trimethylsilyl-ethynyl)-benzoate are dissolved in 30 ml of methanol, combined with 46.7 ml (93.4 mmol) 2-molar potassium hydroxide solution and refluxed for 2 hours. After the elimination of volatile constituents in vacuo the residue is diluted with demineralised water and acidified with 2-molar hydrochloric acid solution. The aqueous phase is extracted three times with ethyl acetate, the combined organic phases are dried over sodium sulphate and then the solvent is eliminated in vacuo.

[0493] Yield: 3.14 g (55%)

[0494] R_(f) value: 0.59 (silica gel; dichloromethane/ethanol=4:1)

[0495] C₁₄H₁₃NO₃ (243.27)

[0496] Mass spectrum: (M+H)⁺=244

[0497] (e) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-ethynyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0498] Prepared analogously to Example 1g from 3-ethynyl-4-(pyrrolidin-1-ylcarbonyl)-benzoic acid, TBTU, diisopropylethylamine and rac-1-(5-chloro-benzimidazol-2-yl)ethylamine in tetrahydrofuran.

[0499] Yield: 46%

[0500] R_(f) value: 0.48 (silica gel; dichloromethane/ethanol=9:1)

[0501] C₂₃H₂₁ClN₄O₂ (420.90)

[0502] Mass spectrum: (M+H)⁺=421/423 (chlorine isotope)

EXAMPLE 7

[0503] N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-ethyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0504] 60 mg (0.143 mmol) of N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-ethynyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide are dissolved in 6.0 ml dioxane/water=1:1, combined with 8.0 mg platinum/activated charcoal and hydrogenated for 7 hours with hydrogen (3 bar). Then the catalyst is filtered off and the solvent is distilled off.

[0505] Yield: 99%

[0506] R_(f) value: 0.15 (Reversed-phase-8; methanol/5%-NaCl solution=3:2)

[0507] C₂₃H₂₅ClN₄O₂ (424.93)

[0508] Mass spectrum: (M−H)⁻=423/425 (chlorine isotope) (M+H)⁺=425/427 (chlorine isotope)

EXAMPLE 8

[0509] N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(N-cyclobutyl-N-acetyl-amino)-benzamide

[0510] Prepared analogously to Example 1g from 3-methyl-4-(N-cyclobutyl-N-acetyl-amino)benzoic acid, TBTU, diisopropylethylamine and 1-(5-chloro-benzimidazol-2-yl)ethylamine in tetrahydrofuran.

[0511] Yield: quantitative

[0512] R_(f) value: 0.50 (silica gel; methylene chloride/ethanol=9:1)

[0513] C₂₃H₂₅ClN₄O₂ (424.93)

[0514] Mass spectrum: (M+H)⁺=425/427 (chlorine isotope)

EXAMPLE 9

[0515] N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-chloro-4-[2-(N-tertbutoxycarbonyl-aminomethyl)-pyrrolidin-1-yl-carbonyl]-benzamide

[0516] (a) rac-4-[2-(N-tertbutoxycarbonyl-aminomethyl)-pyrrolidin-1-yl-carbonyl]-3-chloro-benzonitrile

[0517] Prepared analogously to Example 1d from 2-chloro-4-cyano-benzoic acid, TBTU, N,N-diisopropylethylamine and rac-2-(N-tertbutoxycarbonyl-aminomethyl)-pyrrolidine in tetrahydrofuran.

[0518] Yield: quantitative

[0519] R_(f) value: 0.52 (silica gel; dichloromethane/ethanol=95:5) C₁₈H₂₂ClN₃O₃ (363.85)

[0520] Mass spectrum: (M+H)⁺=364/366 (chlorine isotope)

[0521] (b) rac.-4-[2-(N-tertbutoxycarbonyl-aminomethyl)-pyrrolidin-1-yl-carbonyl]-3-chloro-benzoic acid

[0522] 4.08 g (11.2 mmol) of rac-4-[2-(N-tertbutoxycarbonyl-aminomethyl)-pyrrolidin-1-yl-carbonyl]-3-chloro-benzonitrile are stirred for 2 hours at 80° C. in 40 ml of ethanol and 10-molar sodium hydroxide solution. The ethanol is then eliminated in vacuo and the residue diluted with ice water. After the aqueous phase has been washed with diethyl ether the aqueous phase is combined with potassium hydrogen sulphate solution while cooling with ice and extracted three times with ethyl acetate. The combined organic phases are dried over sodium sulphate and then the solvent is eliminated in vacuo.

[0523] Yield: 3.34 g (78%)

[0524] R_(f) value: 0.25 (silica gel; dichloromethane/ethanol=95:5)

[0525] C₁₈H₂₃ClN₂O₅ (382.85)

[0526] Mass spectrum: (M+H)⁺=383/385 (chlorine isotope)

[0527] (c) N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-chloro-4-[2-(N-tertbutoxycarbonyl-aminomethyl)-pyrrolidin-1-yl-carbonyl]-benzamide

[0528] Prepared analogously to Example 1g from rac-3-chloro-4-[2-(N-tertbutoxycarbonylmethylamino)pyrrolidin-1-yl-carbonyl]-benzoic acid, TBTU, diisopropylethylamine and rac-1-(5-chloro-benzimidazol-2-yl)-ethylamine in tetrahydrofuran.

[0529] Yield: quantitative (mixture of all four stereoisomers)

[0530] R_(f) value: 0.50 (silica gel; dichloromethane/ethanol=9:1)

[0531] C₂₂H₂₃ClN₄O₂ (410.91)

[0532] Mass spectrum: (M−H)⁻=409/411 (chlorine isotope)

EXAMPLE 10

[0533] (S)-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-4-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0534] (a) (S)-N′-tertbutoxycarbonyl-N-(2-amino-5-chloro)phenyl-3-(pyridin-4-yl)-alaninamide and (S)-N′-tertbutoxycarbonyl-N-(2-amino-4-chloro)phenyl-3-(pyridin-4-yl)-alaninamide

[0535] 2.70 g (13.1 mmol) of N,N′-dicyclohexylcarbodiimide at ambient temperature are added to a solution of 3.48 g (13.1 mmol) of (S)—N-tertbutoxycarbonyl-3-(pyridin-4-yl)-alanine and 1.87 g (13.1 mmol) of 4-chloro-ortho-phenylenediamine in 75 ml of tetrahydrofuran (analogously to K. Maekawa, J. Ohtani, Agr. Biol. Chem. 1976, 40, 791-799). The mixture is stirred for 16 hours at ambient temperature and then the solvent is distilled off. The residue is combined with water, made alkaline and extracted three times with ethyl acetate. The combined organic phases are dried with sodium sulphate and concentrated. The residue is chromatographed on silica gel, eluting with dichloromethane/methanol (100:5). The corresponding fractions are combined and concentrated by evaporation.

[0536] Yield: 2.03 g (mixture of the regioisomers; 40% of theory)

[0537] R_(f) value: 0.23 (silica gel; dichloromethane/methanol=95:5)

[0538] C₁₉H₂₃ClN₄O₃ (390.87)

[0539] Mass spectrum: (M+H)⁺=391/393 (chlorine isotope)

[0540] (b) (S)—N-tertbutoxycarbonyl-1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-4-yl)-ethylamine

[0541] 2.03 g (5.19 mmol) of the regioisomers (S)-N′-tertbutoxycarbonyl-N-(2-amino-5-chloro)phenyl-3-(pyridin-4-yl)-alaninamide and (S)-N′-tertbutoxycarbonyl-N-(2-amino-4-chloro)phenyl-3-(pyridin-4-yl)-alaninamide obtained above are dissolved in 20 ml glacial acetic acid. The mixture is stirred for 1 hour at 55° C. and then the solvent is distilled off. The residue is combined with 2-molar sodium hydroxide solution and extracted three times with ethyl acetate. The combined organic phases are dried with sodium sulphate and concentrated. The residue is triturated with diisopropylether.

[0542] Yield: 1.88 g (97% of theory)

[0543] R_(f) value: 0.75 (silica gel; dichloromethane/methanol=95:5)

[0544] C₁₉H₂₁ClN₄O₂ (372.86)

[0545] Mass spectrum: (M+H)⁺=373/375 (chlorine isotope)

[0546] (c) (S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-4-Yl)-ethylamine

[0547] 1.88 g (5.04 mmol) of (S)—N-tert.butoxycarbonyl-1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-4-yl)-ethylamine are dissolved in 35 ml dichloromethane and combined with 5 ml trifluoroacetic acid. The mixture is stirred for 16 hours at ambient temperature and then the volatile constituents are distilled off. The residue is made alkaline with 2-molar sodium hydroxide solution, evaporated down and then digested with a little water and ethyl acetate. The crystals thus obtained are dried.

[0548] Yield: 1.38 g (quantitative)

[0549] R_(f) value: 0.09 (silica gel; dichloromethane/methanol=9:1)

[0550] C₁₄H₁₃ClN₄ (272.74)

[0551] Mass spectrum: (M+H)⁺=273/275 (chlorine isotope)

[0552] (d) (S)-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-4-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0553] A solution of 0.150 g (0.579 mmol) of 3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzoic acid, 0.186 g (0.579 mmol) of TBTU and 0.20 ml (1.78 mmol) of N-methylmorpholine in 2 ml N,N-dimethylformamide is stirred for 10 minutes at ambient temperature and then combined with a solution of 0.158 g (0.579 mmol) of (S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-pyridin-4-yl-ethylamine. The reaction mixture is stirred for one day at ambient temperature, then poured onto ice water and extracted three times with ethyl acetate. The combined organic phases are dried with sodium sulphate and concentrated. The residue is chromatographed on silica gel, eluting with dichloromethane/methanol (95:10).

[0554] Yield: 61.5 mg (22% of theory)

[0555] R_(f) value: 0.44 (silica gel; dichloromethane/methanol=9:1)

[0556] C₂₇H₂₆ClN₅O₂ (487.99)

[0557] Mass spectrum: (M−H)⁻=486/488 (chlorine isotope)

EXAMPLE 11

[0558] (S)-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-2-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0559] (a) (S)-N′-tertbutoxycarbonyl-N-(2-amino-5-chloro)phenyl-3-(pyridin-2-yl)-alaninamide and (S)-N′-tertbutoxycarbonyl-N-(2-amino-4-chloro)phenyl-3-(pyridin-2-yl)-alaninamide

[0560] 6.03 g (15.8 mmol) of TBTU and 6.3 ml (44.8 mmol) of triethylamine are added at 0° C. to a solution of 4.00 g (15.0 mmol) of (S)—N-tertbutoxycarbonyl-3-(pyridin-2-yl)-alanine and 2.15 g (15.1 mmol) of 4-chloro-o-phenylenediamine in 90 ml dichloromethane. The mixture is heated to ambient temperature and stirred for 72 hours; then the reaction mixture is poured onto ice water and extracted three times with dichloromethane. The combined organic phases are dried with sodium sulphate and concentrated. The residue is chromatographed on silica gel, eluting with ethyl acetate/petroleum ether (60:40). The corresponding fractions are combined and concentrated by evaporation.

[0561] Yield: 1.36 g (mixture of regioisomers; 23% of theory)

[0562] R_(f) value: 0.19 and 0.28 (silica gel; ethyl acetate/petroleum ether=60:40)

[0563] C₁₉H₂₃ClN₄O₃ (390.87)

[0564] Mass spectrum: (M−H)⁻=389/391 (chlorine isotope)

[0565] (b) (S)—N-tertbutoxycarbonyl-1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-2-yl)-ethylamine

[0566] Prepared analogously to Example 10b from 1.36 g (3.48 mmol) of the mixture of (S)-N′-tertbutoxycarbonyl-N-(2-amino-4-chloro)phenyl-3-(pyridin-2-yl)-alaninamide and (S)-N′-tert.-butoxycarbonyl-N-(2-amino-4-chloro)phenyl-3-(pyridin-2-yl)-alaninamide obtained above.

[0567] Yield: 1.03 g (79% of theory)

[0568] R_(f) value: 0.7 (silica gel; dichloromethane/methanol=9:1)

[0569] C₁₉H₂₁ClN₄O₂ (372.86)

[0570] Mass spectrum: (M−H)⁻=371/373 (chlorine isotope)

[0571] (c) (S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-2-yl)-ethylamine

[0572] Prepared analogously to Example 10c from 1.02 g (2.74 mmol) of (S)—N-tert.-butoxycarbonyl-1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-2-yl)-ethylamine. The crude product is chromatographed on silica gel, eluting with dichloromethane/methanol (90:10).

[0573] Yield: 0.2 g (27% of theory)

[0574] R_(f) value: 0.44 (silica gel; dichloromethane/methanol=9:1)

[0575] C₁₄H₁₃ClN₄ (272.74)

[0576] Mass spectrum: (M+H)⁺=273/275 (chlorine isotope)

[0577] (d) (S)-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-2-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0578] Prepared analogously to Example 10d from 0.20 g (0.733 mmol) of (S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-2-yl)-ethylamine.

[0579] Yield: 149 mg (42% of theory)

[0580] R_(f) value: 0.27 (silica gel; dichloromethane/methanol=95:5)

[0581] C₂₇H₂₆ClN₅O₂ (487.99)

[0582] Mass spectrum: (M−H)⁻=486/488 (chlorine isotope)

EXAMPLE 12

[0583] rac.-N-[1-(5-fluoro-1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0584] A solution of 0.10 g (0.43 mmol) of 3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzoic acid, 0.184 g (0.450 mmol) of 1-(5-fluoro-1H-benzimidazol-2-yl)-ethylamine×2(CF₃COOH) (Prepared analogously to Methods 1a, 10b, 10c) and 0.35 ml (2.50 mmol) of triethylamine in 3 ml dimethylsulphoxide is stirred at ambient temperature and combined with 0.193 g (0.600 mmol) of TBTU. The reaction mixture is stirred for 1 hour at ambient temperature, then diluted with ethyl acetate and washed successively with 10% aqueous citric acid, twice with 2-molar sodium hydroxide solution and with water. The organic phase is dried with sodium sulphate and concentrated. The crude product is taken up in ethyl acetate, precipitated with tert.-butylmethylether and dried.

[0585] Yield: 83 mg (49% of theory)

[0586] R_(f) value: 0.34 (silica gel; ethyl acetate/ethanol=9:1)

[0587] C₂₂H₂₃FN₄O₂ (394.45)

[0588] Mass spectrum: (M+H)⁺=395

EXAMPLE 13

[0589] rac.-N-[1-(5-cyano-1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0590] Prepared analogously to Example 12a from 0.135 g (0.450 mmol) of 1-(5-cyano-1H-benzimidazol-2-yl)-ethylammonium-trifluoroacetate.

[0591] Yield: 23 mg (13% of theory)

[0592] R_(f) value: 0.30 (silica gel; ethyl acetate/ethanol=9:1)

[0593] C₂₃H₂₃N₅O₂ (401.47)

[0594] Mass spectrum: (M+H)⁺=402

EXAMPLE 14

[0595] rac.-N-[1-(5-methoxy-1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0596] Prepared analogously to Example 12a from 86 mg (0.45 mmol) of 1-(5-methoxy-1H-benzimidazol-2-yl)-ethylamine.

[0597] Yield: 41 mg (24% of theory)

[0598] R_(f) value: 0.25 (silica gel; ethyl acetate/ethanol=9:1)

[0599] C₂₃H₂₆N₄O₃ (406.49)

[0600] Mass spectrum: (M+H)⁺=407

EXAMPLE 15

[0601] (S)-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(1H-imidazol-4-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0602] Prepared analogously to Example 10d from (S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-(1H-imidazol-4-yl)-ethylamine and 3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzoic acid.

[0603] Yield: 55% of theory.

[0604] R_(f) value: 0.72 (silica gel; dichloromethane/methanol=4:1)

[0605] C₂₅H₂₅ClN₆O₂ (476.97)

[0606] Mass spectrum: (M+H)⁺=477/479 (chlorine isotope)

EXAMPLE 16

[0607] 4-[(2R/S)-aminomethyl-pyrrolidin-1-yl-carbonyl]-3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-4-yl)-ethyl]-benzamide

[0608] Prepared analogously to Example 10d from rac.-4-[2-(tert.-butoxycarbonylamino-methyl)-pyrrolidin-1-yl-carbonyl]-3-chloro-benzoic acid and (S)-(5-chloro-1H-benzimidazol-2-yl)-2-pyridin-4-yl-ethylamine with subsequent cleaving of the protective group with trifluoroacetic acid analogously to Example 10c.

[0609] Yield: 52 mg (11% over 2 steps)

[0610] R_(f) value: 0.15 (silica gel; dichloromethane/methanol=9:1)

[0611] C₂₇H₂₈Cl₂N₆O₂×2 C₂F₃O₂ (765.50)

[0612] Mass spectrum: (M−H)⁻=537/539/541 (chlorine isotope)

EXAMPLE 17

[0613] N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-chloro-4-(2-aminomethyl-pyrrolidin-1-yl-carbonyl)-benzamide

[0614] 0.25 g (0.446 mmol) of N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-chloro-4-[2-(N-tert.-butoxycarbonyl-aminomethyl)-pyrrolidin-1-yl-carbonyl]-benzamide (Example 9) are dissolved in 10 ml dichloromethane and after the addition of 0.68 ml (8.9 mmol) of trifluoroacetic acid stirred for 1 hour at ambient temperature. After elimination of the volatile constituents in vacuo the residue is taken up in ethyl acetate, the solution washed twice with 2-molar sodium hydroxide solution and three times with demineralised water and dried over sodium sulphate. Finally, the solvent is eliminated in vacuo.

[0615] Yield: 120 mg (58%; mixture of all four stereoisomers)

[0616] R_(f) value: 0.10 (silica gel; dichloromethane/ethanol=9:1)

[0617] C₂₂H₂₃Cl₂N₅O₂ (460.36)

[0618] Mass spectrum: (M+H)⁺=460/462/464 (chlorine isotope)

EXAMPLE 18

[0619] 1-[N-(5-methyl-1H-benzimidazol-2-yl)]-ethyl-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0620] (a) Isomer mixture of rac.-N′-benzyloxycarbonyl-N-(2-amino-4-methyl)phenyl-alaninamide and rac.-N′-benzyloxycarbonyl-N-(2-amino-5-methyl)phenyl-alaninamide

[0621] 1.57 g (7.03 mmol) of rac.-N-benzyloxycarbonylalanine are placed together with 0.86 g (7.03 mmol) of 3,4-diaminotoluene in 100 ml of tetrahydrofuran at 0° C and 1.45 g (7.03 mmol) of N,N-dicyclohexyl-carbodiimide are added slowly with stirring. The mixture is allowed to come up to ambient temperature and then stirred for another 16 hours. Then the precipitate formed is filtered off and the solvent is distilled off in vacuo. The residue is recrystallised from a little ethyl acetate.

[0622] Yield: 1.1 g (48%)

[0623] R_(f) value: 0.50 (silica gel; dichloromethane/ethanol=9:1).

[0624] C₁₈H₂₁N₃O₃ (327.39)

[0625] Mass spectrum: (M+H)⁺=328

[0626] (b) 1-[N-(5-methyl-1H-benzimidazol-2-yl)]-ethyl-3-methyl-4-(pvrrolidin-1-yl-carbonyl)-benzamide

[0627] Prepared analogously to Example 1g from 3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzoic acid, TBTU, diisopropylethylamine and (5-methyl-benzimidazol-2-yl)ethylamine (prepared from the isomer mixture of Example 18a and the synthesis sequence 1b,1c) in tetrahydrofuran.

[0628] Yield: 47%

[0629] R_(f) value: 0.35 (silica gel; dichloromethane/ethanol=9:1)

[0630] C₂₃H₂₆N₄O₂ (390.49)

[0631] Mass spectrum: (M+H)⁺=391

EXAMPLE 19

[0632] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(3-oxo-piperazin-1-yl-carbonyl)-benzamide

[0633] (a) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-methoxycarbonyl-benzamide

[0634] 1.61 g (7.50 mmol) of 3-chloro-4-methoxycarbonyl-benzoic acid are dissolved in 40 ml N,N-dimethylformamide and combined with 1.30 g (8.00 mmol) of N,N′-carbonyldiimidazole and stirred for 15 minutes at ambient temperature under a nitrogen atmosphere. Then 1.0 ml (7.5 mmol) of triethylamine, 1.5 ml (15 mmol) of N-methylmorpholine and 1.69 g (7.75 mmol) of C-(5-chloro-1H-benzimidazol-2-yl)methylamine are added successively and stirred for a further 16 hours at ambient temperature under a nitrogen atmosphere. Then the reaction mixture is poured into 1 l ice water, the precipitate is separated off by filtering, washed with a little demineralised water and dried at 40° C. Finally the product is recrystallised from petroleum ether/ethyl acetate 2:1.

[0635] Yield: 2.40 g (85%)

[0636] R_(f) value: 0.58 (silica gel; dichloromethane/ethanol=9:1).

[0637] C₁₇H₁₃Cl₂N₃O₃ (378.22)

[0638] Mass spectrum: (M−H)⁻=376/78/80 (chlorine isotope)

[0639] (b) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-hydroxycarbonyl-benzamide

[0640] 2.15 g 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-methoxycarbonyl-benzamide are dissolved in 50 ml isopropanol, 50 ml of 1-molar sodium hydroxide solution are added and the mixture is stirred for 3 hours at ambient temperature. Then it is poured into 250 ml ice water and extracted twice with ethyl acetate. The aqueous phase is adjusted to pH 4 with 1-molar hydrochloric acid and the precipitate formed is separated off by filtration. The solid is washed with a little demineralised water and dried at 40° C. Then the solid obtained is treated with 150 ml of solvent mixture comprising petroleum ether/diethyl ether/ethyl acetate and dried again.

[0641] Yield: quantitative

[0642] C₁₆H₁₁Cl₂N₃O₃ (364.19)

[0643] Mass spectrum: (M+H)⁺=364/66/68 (chlorine isotope)

[0644] (c) 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(3-oxo-piperazin-1-yl-carbonyl)-benzamide

[0645] 0.182 g (0.50 mmol) of 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-hydroxycarbonyl-benzamide are dissolved in 5 ml N,N-dimethylformamide and 160.5 mg (0.50 mmol) of TBTU and 85.6 μl (0.50 mmol) of diisopropylethylamine are added successively with stirring at ambient temperature. Then a solution of 50 mg (0.50 mmol) of 2-oxo-piperazine in 5 ml N,N-dimethylformamide is added dropwise and the reaction mixture is stirred for 3 hours at ambient temperature. Then the solvent is eliminated in vacuo and the residue purified by chromatography on silica gel (gradient: dichloromethane/methanol=100:0>93:7).

[0646] Yield: 99 mg (44%)

[0647] C₂₀H₁₇Cl₂N₅O₃ (446.30)

[0648] Mass spectrum: (M+H)⁺=446/448/450 (chlorine isotope)

EXAMPLE 20

[0649] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)4-(4-methyl-3-oxo-piperazin-1-yl-carbonyl)-benzamide

[0650] Prepared analogously to Example 19c from 2-chloro-4-[N-(5-chloro-benzimidazol-2-yl-methyl)-carbamoyl]-benzoic acid, TBTU, diisopropylethylamine and N-methyl-piperazinone in N,N-dimethylformamide.

[0651] Yield: 8.7%

[0652] C₂₁H₁₉Cl₂N₅O₃ (460.32)

[0653] Mass spectrum: (M+H)⁺=460/462/464 (chlorine isotope)

EXAMPLE 21

[0654] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(2-aminomethyl-pyrrolidin-1-yl-carbonyl)-benzamide

[0655] Prepared analogously to Example 19c from 2-chloro-4-[N-(5-chloro-benzimidazol-2-yl-methyl)-carbamoyl]-benzoic acid, TBTU, diisopropylethylamine and 2-(N-tert.-butoxycarbonyl-aminomethyl)-pyrrolidine in N,N-dimethylformamide and subsequent reaction with trifluoroacetic acid and NaOH analogously to Example 17.

[0656] Yield: 104 mg (47% over 2 steps)

[0657] C₂₁H₂₁Cl₂N₅O₂ (446.34)

[0658] Mass spectrum: (M+H)⁺=446/448/450 (chlorine isotope)

EXAMPLE 22

[0659] N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(2,3-dihydro-imidazo[2,1-b]thiazol-5-yl)-benzamide

[0660] (a) 4-(2,3-dihydro-imidazo[2,1-b]thiazol-5-yl)-benzonitrile

[0661] 3.00 g (12.72 mmol) of 4-bromoacetyl-benzonitrile are dissolved in 40 ml acetonitrile, and combined with 2.65 g (25.42 mmol) of 2-amino-4,5-dihydro-thiazole and 2.00 g molecular sieve 4 Å. Then the mixture is stirred for 2.5 days at ambient temperature. Then the solvent is eliminated in vacuo, and the residue is taken up with 100 ml 1-molar hydrochloric acid solution and the insoluble matter is taken up with a little methanol and concentrated ammonia solution. After filtration the filtrate is concentrated in vacuo and purified by chromatography on silica gel (gradient: initially ethyl acetate/ethanol=100:0 40:60+0.5% ammonia, then dichloromethane/methanol=6:4+2% triethylamine).

[0662] Yield: 2.4 g

[0663] R_(f) value: 0.65 (silica gel; ethyl acetate/ethanol=8:2+1% ammonia)

[0664] C₁₂H₉N₃S (227.29)

[0665] Mass spectrum: (M+H)⁺=228

[0666] (b) 4-(2,3-dihydro-imidazo[2,1-b]thiazol-5-yl)-benzoic acid

[0667] 2.00 g (8.80 mmol) of contaminated 4-(2,3-dihydro-imidazo[2,1-b]thiazol-5-yl)-benzonitrile are placed in 60 ml 50% acetic acid solution at 0° C. and slowly combined with 30 ml concentrated sulphuric acid with stirring and cooling in the ice bath. The reaction mixture is heated to 100° C. for 17 hours and then poured into 500 ml ice water. The precipitated product formed is filtered off. The mother liquor is combined with sodium chloride and extracted with 300 ml of ethyl acetate, washed with saturated sodium chloride solution, dried with magnesium sulphate and the solvent is distilled off. The residue remaining is combined with the above precipitate.

[0668] Yield: 1.25 g (40% over 2 steps).

[0669] R_(f) value: 0.55 (silica gel; ethyl acetate/ethanol=9:1)

[0670] C₁₂H₁₀N₂O₂S (246.29)

[0671] Mass spectrum: (M+H)⁺=247

[0672] (c) N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(2,3-dihydro-imidazo[2,1-b]thiazol-5-yl)-benzamide

[0673] Prepared analogously to Example 1g from 4-(2,3-dihydro-imidazo[2,1-b]-thiazol-5-yl)-benzoic acid, TBTU, triethylamine and (5-chloro-1H-benzimidazol-2-yl)-methylamine in N,N-dimethylformamide.

[0674] Yield: 73%

[0675] R_(f) value: 0.50 (silica gel; ethyl acetate/ethanol=9:1)

[0676] C₂₀H₁₆ClN₅OS (409.90)

[0677] Mass spectrum: (M+H)⁺=410/412 (chlorine isotope)

EXAMPLE 23

[0678] 2-(5-chloro-1H-benzimidazol-2-yl)-N-[3-methyl-4-(pyrrolidin-1-yl-carbonyl)-phenyl]-acetamide

[0679] (a) methyl N-(2-amino-4-chloro-phenyl)-carbamoyl-acetate and N-(2-methyl amino-5-chloro-phenyl)-carbamoyl-acetate

[0680] 5.70 g (40.0 mmol) of 4-chloro-o-phenylenediamine are placed in 75 ml dichloromethane, combined with 5.8 ml (42.0 mmol) of triethylamine and while being cooled in the ice bath slowly combined with 3 ml (41.0 ml) of methyl malonate chloride. Then the mixture is heated to ambient temperature and stirred for 24 hours. The reaction mixture is poured into ice water and extracted three times with dichloromethane. The combined organic phases are washed with saturated sodium chloride solution, dried over sodium sulphate and concentrated. The residue is purified by chromatography on silica gel (gradient: petroleum ether/ethyl acetate=9:1->7:3->1:1).

[0681] Yield: 1.15 g (12%)

[0682] R_(f) value: 0.20 (silica gel; petroleum ether/ethyl acetate=1:1)

[0683] C₁₀H₁₁ClN₂O₃ (242.66)

[0684] Mass spectrum: (M+H)⁺=243/245 (chlorine isotope)

[0685] (b) methyl (5-chloro-1H-benzimidazol-2-yl)-acetate

[0686] 1.10 g (4.53 mmol) of methyl N-(2-amino-4-chloro-phenyl)-carbamoyl-acetate and methyl N-(2-amino-5-chloro-phenyl)-carbamoyl-acetate are refluxed for 25 minutes in 25 ml glacial acetic acid. Then the mixture is neutralised cold with concentrated ammonia solution and the precipitate formed is filtered off and dried.

[0687] Yield: 0.78 g (58%) (purity: 75%)

[0688] R_(f) value: 0.30 (silica gel; dichloromethane/ethanol=19:1)

[0689] C₁₀HgClN₂O₂ (224.65)

[0690] Mass spectrum: (M+H)⁺=225/227 (chlorine isotope)

[0691] (c) (5-chloro-1H-benzimidazol-2-yl)-acetic acid-hydrochloride

[0692] 0.68 g (2.27 mmol) of 75% methyl (5-chloro-1H-benzimidazol-2-yl)-acetate are suspended in 20 ml concentrated hydrochloric acid solution and stirred for 16 hours at ambient temperature. The precipitate formed is suction filtered and the filtrate concentrated in vacuo at 50° C. The residue is taken up twice in toluene and twice in diethyl ether, the volatile constituents are eliminated in vacuo. The residue is washed with diethyl ether.

[0693] Yield: 0.23 g (41%) (hydrochloride)

[0694] R_(f) value: 0.15 (silica gel; dichloromethane/ethanol=8:2+1% glacial acetic acid)

[0695] C₉H₇ClN₂O₂×HCl (210.62/247.08)

[0696] Mass spectrum: (M+H)⁺=211/213 (chlorine isotope)

[0697] (d) 2-(5-chloro-1H-benzimidazol-2-yl)-N-[3-methyl-4-(pyrrolidin-1-yl-carbonyl)-phenyl]-acetamide

[0698] Prepared analogously to Example 1g from (5-chloro-1H-benzimidazol-2-yl)-acetic acid, TBTU, N-methylmorpholine and 4-amino-2-methyl-benzoic acid-pyrrolidine-amide in N,N-dimethylformamide and subsequent chromatography on silica gel (gradient: dichloromethane/ethanol=100:0->25:1->19:1->9:1)

[0699] Yield: 14 mg (7.1%)

[0700] R_(f) value: 0.45 (silica gel; dichloromethane/ethanol=9:1)

[0701] C₂₁H₂₁ClN₄O₂ (396.88)

[0702] Mass spectrum: (M−H)⁻=395/397 (chlorine isotope)

EXAMPLE 24

[0703] 3-methyl-4-(pyrrolidine-1-carbonyl)-N-[1-(5-trifluoromethyl-1H-benzimidazol-2-yl)-ethyl]-benzamide

[0704] Prepared analogously to Example 10d from 3-methyl-4-(pyrrolidin-1-yl-carbonyl)benzoic acid, TBTU, diisopropylethylamine and rac.-1-(5-trifluoromethyl-1H-benzimidazol-2-yl)-ethylamine in dimethylformamide.

[0705] Yield: 90 mg (47% of theory)

[0706] R_(f) value: 0.38 (silica gel; ethyl acetate/ethanol=9:1)

[0707] C₂₃H₂₃F₄N₃O₂ (444.46)

[0708] Mass spectrum: (M+H)⁺=445

EXAMPLE 25

[0709] (S)-N-[2-aminocarbonyl-1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0710] Prepared analogously to Example 10d from 3-methyl-4-(pyrrolidin-1-yl-carbonyl)benzoic acid, TBTU, diisopropylethylamine and (S)-3-amino-3-(5-chloro-1H-benzimidazol-2-yl)-propionic acid amide in dimethylformamide.

[0711] Yield: 97 mg (43% of theory)

[0712] R_(f) value: 0.37 (silica gel; dichloromethane/methanol=9:1)

[0713] C₂₃H₂₄ClN₅O₃ (453.93)

[0714] Mass spectrum: (M+H)⁺=454/456 (chlorine isotope)

EXAMPLE 26

[0715] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)4-(2,5-dihydropyrrol-1-yl-carbonyl)-benzamide

[0716] Prepared analogously to Example 1d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide and 2,5-dihydropyrrole, TBTU and triethylamine in DMSO.

EXAMPLE 27

[0717] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(thiazolidin-3-yl-carbonyl)-benzamide

[0718] Prepared analogously to Example 1 d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, thiazolidine, TBTU and triethylamine in DMSO at ambient temperature.

[0719] HPLC-MS results

[0720] retention time: 3.51 min

[0721] C₁₉H₁₆Cl₂N₄O₂S (435.33)

[0722] Mass spectrum: (M+H)⁺=435.1

EXAMPLE 28

[0723] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(1,2,3,6-tetrahydro-piperidin-1-yl-carbonyl)-benzamide

[0724] Prepared analogously to Example 1 d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, 1,2,3,6-tetrahydropyridine, TBTU and triethylamine in DMSO at ambient temperature.

[0725] HPLC-MS results

[0726] retention time 3.61 min

[0727] C₂₁H₁₈Cl₂N₄O₂ (429.31)

[0728] Mass spectrum: (M+H)⁺=429.1

EXAMPLE 29

[0729] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(2-methyl-thiomorpholin-4-yl-carbonyl)-benzamide

[0730] Prepared analogously to Example 1 d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, 2-methylthiomorpholine, TBTU and triethylamine in DMSO at ambient temperature.

[0731] HPLC-MS results

[0732] retention time 3.78 min

[0733] C₂₁H₂₀Cl₂N₄O₂S (463.39)

[0734] Mass spectrum: (M+H)⁺=463.1

EXAMPLE 30

[0735] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)4-(thiomorpholin-4-yl-carbonyl)-benzamide

[0736] Prepared analogously to Example 1 d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, thiomorpholine, TBTU and triethylamine in DMSO at ambient temperature.

[0737] HPLC-MS results

[0738] retention time 3.60 min

[0739] C₂₀H₁₈Cl₂N₄O₂S (449.36)

[0740] Mass spectrum: (M+H)⁺=449.1

EXAMPLE 31

[0741] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(N-isopropyl-N-methyl-aminocarbonyl)-benzamide

[0742] Prepared analogously to Example 1 d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, N-isopropyl-methylamine, TBTU and triethylamine in DMSO at ambient temperature.

[0743] HPLC-MS results

[0744] retention time 3.49 min

[0745] C₂₀H₂₀Cl₂N₄O₂ (419.31)

[0746] Mass spectrum: (M+H)⁺=419.2

EXAMPLE 32

[0747] (R)-3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(2-methoxymethyl-pyrrolidin-1-yl-carbonyl)-benzamide

[0748] Prepared analogously to Example 1 d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, (R)-2-methoxymethyl-pyrrolidine, TBTU and triethylamine in DMSO at ambient temperature.

[0749] HPLC-MS results

[0750] retention time 3.56 min

[0751] C₂₂H₂₂Cl₂N₄O₃ (461.35)

[0752] Mass spectrum: (M+H)⁺=461.2

EXAMPLE 33

[0753] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-[3-(pyrrolidin-1-yl-methyl)-piperidin-1-yl-carbonyl]-benzamide

[0754] Prepared analogously to Example 1 d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, 3-(pyrrolidin-1-yl-methyl)-piperidine, TBTU and triethylamine in DMSO at ambient temperature.

[0755] HPLC-MS results

[0756] retention time 3.05 min

[0757] C₂₆H₂₉Cl₂N₅O₂ (514.45)

[0758] Mass spectrum: (M+H)⁺=514.2

EXAMPLE 34

[0759] (S)-3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(2-methoxymethyl-pyrrolidin-1-yl-carbonyl)-benzamide

[0760] Prepared analogously to Example 1 d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, (S)-2-methoxymethyl-pyrrolidine, TBTU and triethylamine in DMSO at ambient temperature.

[0761] HPLC-MS results

[0762] retention time 3.56 min

[0763] C₂₂H₂₂Cl₂N₄O₃ (461.35)

[0764] Mass spectrum: (M+H)⁺=461.1

EXAMPLE 35

[0765] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(azetidin-1-yl-carbonyl)-benzamide

[0766] Prepared analogously to Example 1 d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, azetidine, TBTU and triethylamine in DMSO at ambient temperature.

[0767] HPLC-MS results

[0768] retention time 3.25 min

[0769] C₁₉H₁₆Cl₂N₄O₃ (403.27)

[0770] Mass spectrum: (M+H)⁺=403.1

EXAMPLE 36

[0771] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(2-methyl-pyrrolidin-1-yl-carbonyl)-benzamide

[0772] Prepared analogously to Example 1d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, 2-methyl-pyrrolidine, TBTU and triethylamine in DMSO at ambient temperature.

[0773] HPLC-MS results

[0774] retention time 3.62 min

[0775] C₂₁H₂₀Cl₂N₄O₂ (431.32)

[0776] Mass spectrum: (M+H)⁺=431.2

EXAMPLE 37

[0777] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(N-isobutyl-N-methyl-aminocarbonyl)-benzamide

[0778] Prepared analogously to Example 1 d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, N-isobutyl-methylamine, TBTU and triethylamine in DMSO at ambient temperature.

EXAMPLE 38

[0779] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-([1,4]oxazepan-1-yl-carbonyl)-benzamide

[0780] Prepared analogously to Example 1d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, [1,4]oxazepan, TBTU and triethylamine in DMSO at ambient temperature.

[0781] HPLC-MS results

[0782] retention time 3.28 min

[0783] C₂₁H₂₀Cl₂N₄O₃ (447.32)

[0784] Mass spectrum: (M+H)⁺=447.2

EXAMPLE 39

[0785] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(2,5-dimethyl-pyrrolidin-1-yl-carbonyl)-benzamide

[0786] Prepared analogously to Example 1d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, 2,5-dimethyl-pyrrolidine, TBTU and triethylamine in DMSO at ambient temperature.

[0787] HPLC-MS results

[0788] retention time 3.77 min

[0789] C₂₂H₂₂Cl₂N₄O₂ (445.35)

[0790] Mass spectrum: (M+H)⁺=445.2

EXAMPLE 40

[0791] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(piperidin-1-yl-carbonyl)-benzamide

[0792] Prepared analogously to Example 1d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, piperidine, TBTU and triethylamine in DMSO at ambient temperature.

[0793] HPLC-MS results

[0794] retention time 3.65 min

[0795] C₂₁H₂₀Cl₂N₄O₂ (431.32)

[0796] Mass spectrum: (M+H)⁺=431.2

EXAMPLE 41

[0797] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(4-hydroxy-piperidin-1-yl-carbonyl)-benzamide

[0798] Prepared analogously to Example 1d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, 4-hydroxypiperidine, TBTU and triethylamine in DMSO at ambient temperature.

[0799] HPLC-MS results

[0800] retention time 3.09 min

[0801] C₂₁H₂₀Cl₂N₄O₃ (447.32)

[0802] Mass spectrum: (M+H)⁺=447.2

EXAMPLE 42

[0803] 4-(4-acetyl-piperazin-1-yl-carbonyl)-3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-benzamide

[0804] Prepared analogously to Example 1d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)4-carboxy-benzamide, N-acetyl-piperazine, TBTU and triethylamine in DMSO at ambient temperature.

[0805] HPLC-MS results

[0806] retention time 3.13 min

[0807] C₂₂H₂₁Cl₂N₅O₃ (474.35)

[0808] Mass spectrum: (M+H)⁺=474.2

EXAMPLE 43

[0809] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0810] Prepared analogously to Example 1d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, pyrrolidine, TBTU and triethylamine in DMSO at ambient temperature.

[0811] HPLC-MS results

[0812] retention time 3.43 min

[0813] C₂₀H₁₈Cl₂N₄O₂ (417.29)

[0814] Mass spectrum: (M+H)⁺=417.2

EXAMPLE 44

[0815] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(N,N-diethyl-aminocarbonyl)-benzamide

[0816] Prepared analogously to Example 1d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, diethylamine, TBTU and triethylamine in DMSO at ambient temperature.

[0817] HPLC-MS results

[0818] retention time 3.59 min

[0819] C₂₀H₂₀Cl₂N₄O₂ (419.31)

[0820] Mass spectrum: (M+H)⁺=419.2

EXAMPLE 45

[0821] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(3-methyl-piperidin-1-yl-carbonyl)-benzamide

[0822] Prepared analogously to Example 1 d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, 3-methyl-piperidine, TBTU and triethylamine in DMSO at ambient temperature.

[0823] HPLC-MS results

[0824] retention time 3.87 min

[0825] C₂₂H₂₂Cl₂N₄O₂ (445.35)

[0826] Mass spectrum: (M+H)⁺=445.2

EXAMPLE 46

[0827] 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-(4-methyl-piperidin-1-yl-carbonyl)-benzamide

[0828] Prepared analogously to Example 1d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, 4-methyl-piperidine, TBTU and triethylamine in DMSO at ambient temperature.

[0829] HPLC-MS results

[0830] retention time 3.90 min

[0831] C₂₂H₂₂Cl₂N₄O₂ (445.35)

[0832] Mass spectrum: (M+H)⁺=445.2

EXAMPLE 47

[0833] 4-(2-aminomethyl-piperidin-1-yl-carbonyl)-3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-benzamide

[0834] Prepared analogously to Example 1 d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, tert.-butyl piperidin-2-yl-methyl-carbamate, TBTU and triethylamine in DMSO at ambient temperature followed by Boc cleaving with trifluoroacetic acid analogously to Example 17.

EXAMPLE 48

[0835] 4-(3-aminomethyl-piperidin-1-yl-carbonyl)-3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-benzamide

[0836] Prepared analogously to Example 1 d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, tert.butyl piperidin-3-yl-methyl-carbamate, TBTU and triethylamine in DMSO at ambient temperature followed by Boc cleaving with trifluoroacetic acid analogously to Example 17.

[0837] HPLC-MS results

[0838] retention time 2.96 min

[0839] C₂₂H₂₃Cl₂N₅O₂ (460.36)

[0840] Mass spectrum: (M+H)⁺=460.2

EXAMPLE 49

[0841] 4-[3-(2-amino-ethyl)-piperidin-1-yl-carbonyl]-3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-benzamide

[0842] Prepared analogously to Example 1 d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, tert.butyl (2-piperidin-3-yl-ethyl)-carbamate, TBTU and triethylamine in DMSO at ambient temperature followed by Boc cleaving with trifluoroacetic acid analogously to Example 17.

[0843] HPLC-MS results

[0844] retention time 3.01 min

[0845] C₂₃H₂₅Cl₂N₅O₂ (474.39)

[0846] Mass spectrum: (M+H)⁺=474.2

EXAMPLE 50

[0847] 4-(2-aminomethyl-pyrrolidin-1-yl-carbonyl)-3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-benzamide

[0848] Prepared analogously to Example 1d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, tert.butyl pyrrolidin-2-yl-methyl-carbamate, TBTU and triethylamine in DMSO at ambient temperature followed by Boc cleaving with trifluoroacetic acid analogously to Example 17.

[0849] HPLC-MS results

[0850] retention time 2.98 min

[0851] C₂₁H₂₁Cl₂N₅O₂ (446.34)

[0852] Mass spectrum: (M+H)⁺=446.2

EXAMPLE 51

[0853] 4-(3-amino-piperidin-1-yl-carbonyl)-3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-benzamide

[0854] Prepared analogously to Example 1 d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, tert.butyl piperidin-3-yl-carbamate, TBTU and triethylamine in DMSO at ambient temperature followed by Boc cleaving with trifluoroacetic acid analogously to Example 17.

[0855] HPLC-MS results

[0856] retention time 2.91 min

[0857] C₂₁H₂₁Cl₂N₅O₂ (446,34)

[0858] Mass spectrum: (M+H)⁺=446.2

EXAMPLE 52

[0859] N-(6-chloro-quinolin-2-ylmethyl)-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0860] (a) 6-chloro-quinoline-2-carbaldehyde-oxime

[0861] 0.33 g (4.8 mmol) of hydroxylamine hydrochloride and then 0.9 ml (4.6 mmol) of triethylamine are added to a solution of 0.83 g (4.34 mmol) of 6-chloro-quinoline-2-carbaldehyde in 20 ml DMF/ethanol (v/v 1:1). The reaction mixture is stirred for 16 hours at ambient temperature; then it is poured onto water. The precipitated solid is filtered off and dried.

[0862] Yield: 0.79 g (88% of theory)

[0863] R_(f) value: 0.73 (silica gel; dichloromethane/methanol=9:1)

[0864] C₁₀H₇ClN₂O (206.63)

[0865] Mass spectrum: (M+H)⁺=407/209 (chlorine isotope)

[0866] (b) C-(6-chloro-quinolin-2-yl)-methylamine

[0867] A solution of 0.78 g (3.79 mmol) of 6-chloro-quinoline-2-carbaldehyde-oxime in 30 ml of saturated ammoniacal methanol and 10 ml of tetrahydrofuran is hydrogenated with Raney nickel for 48 hours at 3 bar hydrogen pressure. The catalyst is filtered off and the solution is concentrated. The residue is chromatographed on silica gel, eluting with a gradient of dichloromethane/methanol (90:10) to dichloromethane/methanol/25% aqueous ammonia (90:10:1). The corresponding fractions are combined and concentrated by evaporation.

[0868] Yield: 0.33 g (45% of theory)

[0869] R_(f) value: 0.43 (silica gel; dichloromethane/methanol=9:1)

[0870] C₁₀HgClN₂ (192.65)

[0871] Mass spectrum: (M+H)⁺=193/195 (chlorine isotope)

[0872] (c) N-(6-chloro-quinolin-2-ylmethyl)-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0873] Prepared analogously to Example 10d from 0.16 g (0.83 mmol) of C-(6-chloro-quinolin-2-yl)-methylamine.

[0874] Yield: 135 mg (40% of theory)

[0875] R_(f) value: 0.40 (silica gel; dichloromethane/ethanol=100:5)

[0876] C₂₃H₂₂ClN₃O₂ (407.90)

[0877] Mass spectrum: (M+H)⁺=408/410 (chlorine isotope)

EXAMPLE 53

[0878] N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-N-ethyl-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0879] Prepared analogously to Example 1g from 3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzoic acid, TBTU, diisopropylethylamine and N-[1-(5-chloro-benzimidazol-2-yl)ethyl]-ethylamine in tetrahydrofuran.

[0880] Yield: 36%

[0881] R_(f) value: 0.45 (silica gel; dichloromethane/ethanol=9:1)

[0882] C₂₄H₂₇ClN₄O₂ (438.96)

[0883] Mass spectrum: (M−H)⁻=437/439 (chlorine isotope)

EXAMPLE 54

[0884] N-(6-bromo-3H-imidazo[4,5-b]pyridin-2-yl)methyl-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0885] (a) NA-(tert.-butoxycarbonyl)-N-(5-bromo-3-nitro-pyridin-2-yl)glycinamide

[0886] 7.80 g (44.49 mmol) of N-tert.-butoxycarbonyl-glycine are placed together with 7.94 g (48.9 mmol) of N,N′-carbonyldiimidazole in 40 ml N,N-dimethylformamide under a nitrogen atmosphere and combined successively with 10 g (44.5 mmol) of 2-amino-5-bromo-3-nitro-pyridine and 10.8 ml (97.9 mmol) of N-methylmorpholine. Then the reaction mixture is stirred for 2.5 days at ambient temperature. It is then heated to 100° C. for 1 hour and refluxed for 4 hours, then left to cool to ambient temperature and stirred for a further 16 hours. The reaction mixture is concentrated in vacuo, combined with dichloromethane and demineralised water and stirred for 20 minutes. The precipitate formed is removed by filtration, the organic phase is dried over sodium sulphate and the solvent eliminated in vacuo.

[0887] Yield: 4.71 g (49%)

[0888] (b) NA-(tert.-butoxycarbonyl)-N-(5-bromo-3-amino-pyridin-2-yl)glycinamide

[0889] 2.74 g of the product obtained above are dissolved in 70 ml of ethyl acetate, combined with 13.88 g (61.5 mmol) of tin(II)chloride and refluxed for 1 hour. The reaction mixture is cooled to ambient temperature and then poured into a solution of 12.7 g (150 mmol) of sodium hydrogen carbonate in 400 ml ice water. After filtration the organic phase is dried over sodium sulphate and the solvent is eliminated in vacuo.

[0890] Yield: 1.62 g (69%)

[0891] R_(f) value: 0.63 (RP8; methanol/5% sodium chloride solution 6:4)

[0892] C₁₂H₁₇BrN₄O₃ (345.20)

[0893] Mass spectrum: (M−H)⁻=188/190 (bromine isotope)

[0894] (c) N-(6-bromo-3H-imidazo[4,5-b]pyridin-2-yl)methyl-acetamide

[0895] 3.19 g (9.24 mmol) of N′-(tert.-butoxycarbonyl)-N-(5-bromo-3-amino-pyridin-2-yl)glycinamide are refluxed for 4 hours in 15 ml glacial acetic acid under an argon atmosphere. The reaction mixture is concentrated in vacuo and the residue is treated with diethyl ether. The crystals are filtered off and dried.

[0896] Yield: 2.03 g (82%), purity 55%.

[0897] R_(f) value: 0.13 (silica gel; dichloromethane/ethanol=9:1) C₉H₉BrN₄O (269.10)

[0898] Mass spectrum: (M+H)⁺=269/271 (bromine isotope)

[0899] (d) C-(6-bromo-3H-imidazo[4,5-b]pyridin-2-yl)methylamine

[0900] 2.03 g (7.54 mmol) of N-(6-bromo-3H-imidazo[4,5-b]pyridin-2-yl)methyl-acetamide are combined with 30 ml of 6-molar hydrochloric acid solution in 15 ml of ethanol and heated to 40° C. for 2 hours. After cooling to ambient temperature the mixture is extracted with dichloromethane, and the organic phase is extracted with 5% sodium hydrogen carbonate solution. The aqueous phase is concentrated in vacuo and the residue treated with diethyl ether. After the solvent has been eliminated in vacuo the residue is combined with 30 ml of 6-molar hydrochloric acid solution and heated to 50° C. for 16 hours. After elimination of the solvent the residue is twice taken up in methanol and in each case concentrated in vacuo. The crystals formed are washed with methanol and dried at 50° C.

[0901] Yield: 560 mg (28%; hydrochloride).

[0902] R_(f) value: 0.15 (silica gel; dichloromethane/ethanol=9:1+2% ammonia solution)

[0903] C₇H₇BrN₄×HCl (227.06/263.53)

[0904] Mass spectrum: (M−H)⁻=225/227 (bromine isotope)

[0905] (e) N-(6-bromo-3H-imidazo[4,5-b]pyridin-2-yl)methyl-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0906] Prepared analogously to Example 1g from C-(6-bromo-3H-imidazo[4,5-b]pyridin-2-yl)methylamine, TBTU, diisopropylethylamine and 3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzoic acid in tetrahydrofuran.

[0907] Yield: 190 mg (76%)

[0908] R_(f) value: 0.67 (silica gel; dichloromethane/ethanol=8:2+2% ammonia solution)

[0909] C₂₀H₂₀BrN₅O₂ (442,32)

[0910] Mass spectrum: (M+H)⁺=442/444 (bromine isotope)

EXAMPLE 55

[0911] N-(6-bromo-3H-imidazo[4,5-b]pyridin-2-yl)methyl-3-methyl-4-(2,5-dihydropyrrol-1-yl-carbonyl)-benzamide

[0912] Prepared analogously to Example 1g from C-(6-bromo-3H-imidazo[4,5-b]pyridin-2-yl)methylamine, TBTU, diisopropylethylamine and 3-methyl-4-(2,5-dihydropyrrol-1-yl-carbonyl)-benzoic acid in tetrahydrofuran. Purification is effected by chromatography on silica gel (gradient: dichloromethane/ethanol=100:0->80:20).

[0913] Yield: 240 mg (96%)

[0914] R_(f) value: 0.68 (silica gel; dichloromethane/ethanol=8:2+2% ammonia solution)

[0915] C₂₀H₁₈BrN₅O₂ (440.30)

[0916] Mass spectrum: (M+H)⁺=440/442 (bromine isotope)

EXAMPLE 56

[0917] N-[1-(5-bromo-1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0918] Prepared analogously to Example 1g from 3-methyl-4-(pyrrolidin-1-yl-carbonyl)benzoic acid, TBTU, diisopropylethylamine and 1-(5-bromo-1H-benzimidazol-2-yl)ethylamine in tetrahydrofuran.

[0919] Yield: 49%

[0920] R_(f) value: 0.52 (silica gel; methylene chloride/ethanol=9:1)

[0921] C₂₂H₂₃BrN₄O₂ (455.35)

[0922] Mass spectrum: (M+H)⁺=455/457 (bromine isotope)

EXAMPLE 57

[0923] N-[(5-chloro-1H-benzimidazol-2-yl)-phenyl-methyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0924] Prepared analogously to Example 1g from 3-methyl-4-(pyrrolidin-1-yl-carbonyl)benzoic acid, TBTU, diisopropylethylamine and C-(5-chloro-benzimidazol-2-yl)-C-phenyl-methylamine in tetrahydrofuran.

[0925] Yield: quantitative

[0926] R_(f) value: 0.59 (silica gel; methylene chloride/ethanol=9:1)

[0927] C₂₇H₂₅ClN₄O₂ (472.97)

[0928] Mass spectrum: (M+H)⁺=473 (M−H)⁻=471

EXAMPLE 58

[0929] N-[1-(1H-benzimidazol-2-yl)-ethyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0930] Prepared analogously to Example 1g from 3-methyl-4-(pyrrolidin-1-yl-carbonyl)benzoic acid, TBTU, diisopropylethylamine and 1-(1H-benzimidazol-2-yl)-ethylamine in tetrahydrofuran.

[0931] Yield: 83%

[0932] R_(f) value: 0.67 (silica gel; methylene chloride/ethanol=9:1)

[0933] C₂₂H₂₄N₄O₂ (376.46)

[0934] Mass spectrum: (M+H)⁺=377

EXAMPLE 59

[0935] N-[1-(5-chloro-1H-benzimidazol-2-yl)-5-benzyloxycarbonylamino-pentyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0936] Prepared analogously to Example 1g from 3-methyl-4-(pyrrolidin-1-yl-carbonyl)benzoic acid, TBTU, diisopropylethylamine and 1-(5-chloro-1H-benzimidazol-2-yl)-5-benzyloxycarbonylamino-pentylamine in tetrahydrofuran.

[0937] Yield: quantitative

[0938] R_(f) value: 0.52 (silica gel; methylene chloride/ethanol=9:1)

[0939] C₃₃H₃₆ClN₅O₄ (602.13)

[0940] Mass spectrum: (M−H)⁻=600/602 (chlorine isotope)

EXAMPLE 60

[0941] N-[1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-chloro-4-(3-oxo-piperazin-1-yl-carbonyl)-benzamide

[0942] Prepared analogously to Example 1d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-hydroxycarbonyl-benzamide, TBTU, diisopropylethylamine and 2-oxo-piperazine in tetrahydrofuran.

[0943] Yield: 36%

[0944] R_(f) value: 0.75 (silica gel; methylene chloride/ethanol=4:1)

[0945] C₂₁H₁₉Cl₂N₅O₃ (460.32)

[0946] Mass spectrum: (M+H)⁺=460/462/464 (chlorine isotope)

EXAMPLE 61

[0947] N-[1-(5-chloro-1H-benzimidazol-2-yl)-3-methyl-butyl]-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0948] Prepared analogously to Example 1g from 3-methyl-4-(pyrrolidin-1-yl-carbonyl)benzoic acid, TBTU, diisopropylethylamine and 1-(5-chloro-1H-benzimidazol-2-yl)-3-methyl-butylamine in tetrahydrofuran.

[0949] Yield: 82%

[0950] R_(f) value: 0.54 (silica gel; methylene chloride/ethanol=9:1)

[0951] C₂₅H₂₉ClN₄O₂ (452.98)

[0952] Mass spectrum: (M+H)⁺ 453/455 (chlorine isotope) (M−H)⁻=451/453 (chlorine isotope)

EXAMPLE 62

[0953] N-[1-(5-chloro-1H-benzimidazol-2-yl)]ethyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0954] Prepared analogously to Example 1g from 4-(pyrrolidin-1-yl-carbonyl)benzoic acid, TBTU, diisopropylethylamine and 1-(5-chloro-1H-benzimidazol-2-yl)ethylamine in tetrahydrofuran.

[0955] Yield: 98%

[0956] R_(f) value: 0.50 (silica gel; methylene chloride/ethanol=9:1)

[0957] C₂₁H₂₁ClN₄O₂ (396.88)

[0958] Mass spectrum: (M+H)⁺=397/399 (chlorine isotope)

EXAMPLE 63

[0959] (S)-N-[1-(5-chloro-1H-benzimidazol-2-yl)]ethyl-3-methyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0960] Prepared analogously to Example 1g from 3-methyl-4-(pyrrolidin-1-yl-carbonyl)benzoic acid, TBTU, diisopropylethylamine and (S)-1-(5-chloro-benzimidazol-2-yl)ethylamine in tetrahydrofuran.

[0961] Yield: 76%

[0962] R_(f) value: 0.50 (silica gel; methylene chloride/ethanol=9:1)

[0963] C₂₂H₂₃ClN₄O₂ (410.91)

[0964] Mass spectrum: (M−H)⁻=409/411 (chlorine isotope)

EXAMPLE 64

[0965] rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)]ethyl-3-chloro-4-[N-(2-dimethylamino)ethyl-N-ethyl-aminocarbonyl]-benzamide

[0966] Prepared analogously to Example 1 d from 3-chloro-N-(5-chloro-1H-benzimidazol-2-yl-methyl)-4-carboxy-benzamide, TBTU, diisopropylethylamine and N-(2-dimethylamino)ethyl-ethylamine in tetrahydrofuran.

[0967] Yield: 99%

[0968] R_(f) value: 0.10 (silica gel; methylene chloride/ethanol=9:1)

[0969] C₂₃H₂₇Cl₂N₅O₂ (476.40)

[0970] Mass spectrum: (M+H)⁺=476/478/479 (chlorine isotope) (M−H)⁻=474/476/477 (chlorine isotope)

EXAMPLE 65

[0971] rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)]ethyl-3-bromo-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0972] Prepared analogously to Example 1g from 3-bromo-4-(pyrrolidin-1-yl-carbonyl)benzoic acid, TBTU, diisopropylethylamine and rac.-1-(5-chloro-1H-benzimidazol-2-yl)ethylamine in tetrahydrofuran.

[0973] Yield: 73%

[0974] R_(f) value: 0.50 (silica gel; methylene chloride/ethanol=9:1)

[0975] C₂₁H₂₀BrClN₄O₂ (475.78)

[0976] Mass spectrum: (M−H)⁻=473/475/477 (bromine/chlorine isotope)

EXAMPLE 66

[0977] rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)]ethyl-3-trifluoromethyl-4-(pyrrolidin-1-yl-carbonyl)-benzamide

[0978] Prepared analogously to Example 1g from 3-trifluoromethyl-4-(pyrrolidin-1-yl-carbonyl)benzoic acid, TBTU, diisopropylethylamine and rac.-1-(5-chloro-1H-benzimidazol-2-yl)ethylamine in tetrahydrofuran.

[0979] Yield: quantitative

[0980] R_(f) value: 0.50 (silica gel; methylene chloride/ethanol=9:1)

[0981] C₂₂H₂₀ClF₃N₄O₂ (464.88)

[0982] Mass spectrum: (M−H)⁻=463/465 (chlorine isotope)

EXAMPLE 67

[0983] 4-(2-aminomethyl-pyrrolidin-1-yl-carbonyl)-N-[2-aminocarbonyl-1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-chloro-benzamide

[0984] Prepared analogously to Example 17 from 4-[2-(N-tert.-butoxycarbonyl-aminomethyl)-pyrrolidine-1-carbonyl]-N-[2-aminocarbonyl-1-(5-chloro-1H-benzimidazol-2-yl)-ethyl]-3-chloro-benzamide and trifluoroacetic acid.

[0985] Yield: 59% (mixture of all four stereoisomers)

[0986] R_(f) value: 0.23 (silica gel; dichloromethane/methanol=7:3)

[0987] C₂₃H₂₄Cl₂N₆O₃ (503.39)

[0988] Mass spectrum: (M+H)⁺=503/505/507 (chlorine isotope)

EXAMPLE 68

[0989] 4-(2-aminomethyl-pyrrolidin-1-yl-carbonyl)-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(1H-imidazol-4-yl)-ethyl]-benzamide

[0990] Prepared analogously to Example 17 from 4-[2-(N-tert.-butoxycarbonyl-aminomethyl)-pyrrolidin-1-yl-carbonyl]-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(1H-imidazol-4-yl)-ethyl]-benzamide and trifluoroacetic acid.

[0991] Yield: 98% of theory

[0992] R_(f) value: 0.47 (silica gel; dichloromethane/methanol=7:3)

[0993] C₂₅H₂₅Cl₂N₇O₂ (526.43)

[0994] Mass spectrum: (M+H)⁺=526/528/530 (chlorine isotope)

EXAMPLE 69

[0995] 4-(2-aminomethyl-pyrrolidin-1-yl-carbonyl)-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-2-yl)-ethyl]-benzamide

[0996] Prepared analogously to Example 17 from 4-[2-(N-tert.-butoxycarbonyl-aminomethyl)-pyrrolidin-1-yl-carbonyl]-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-2-yl)-ethyl]-benzamide and trifluoroacetic acid.

[0997] Yield: 216 mg (85%, mixture of four stereoisomers)

[0998] R_(f) value: 0.27 (silica gel; dichloromethane/methanol/ammonia=9:1:0.1)

[0999] C₂₇H₂₆Cl₂N₆O₂ (537.45)

[1000] Mass spectrum: (M−H)⁻=535/537/539 (chlorine isotope)

[1001] The Examples that follow describe the preparation of pharmaceutical formulations which contain as active substance any desired compound of general formula (I):

EXAMPLE I

[1002] Dry ampoule containing 75 mg of active substance per 10 ml

[1003] Composition: Active substance 75.0 mg Mannitol 50.0 mg water for injections ad 10.0 ml

[1004] Preparation:

[1005] Active substance and mannitol are dissolved in water. After packaging the solution is freeze-dried. To produce the solution ready for use for injections, the product is dissolved in water.

EXAMPLE II

[1006] Dry ampoule containing 35 mg of active substance per 2 ml

[1007] Composition: Active substance 35.0 mg Mannitol 100.0 mg water for injections ad 2.0 ml

[1008] Preparation:

[1009] Active substance and mannitol are dissolved in water. After packaging, the solution is freeze-dried.

[1010] To produce the solution ready for use for injections, the product is dissolved in water.

EXAMPLE III

[1011] Tablet containing 50 mg of active substance

[1012] Composition: (1) Active substance  50.0 mg (2) Lactose  98.0 mg (3) Maize starch  50.0 mg (4) Polyvinylpyrrolidone  15.0 mg (5) Magnesium stearate  2.0 mg 215.0 mg

[1013] Preparation:

[1014] (1), (2) and (3) are mixed together and granulated with an aqueous solution of (4). (5) is added to the dried granulated material. From this mixture tablets are pressed, biplanar, faceted on both sides and with a dividing notch on one side.

[1015] Diameter of the tablets: 9 mm.

EXAMPLE IV

[1016] Tablet containing 350 mg of active substance

[1017] Composition: (1) Active substance 350.0 mg (2) Lactose 136.0 mg (3) Maize starch  80.0 mg (4) Polyvinylpyrrolidone  30.0 mg (5) Magnesium stearate  4.0 mg 600.0 mg

[1018] Preparation:

[1019] (1), (2) and (3) are mixed together and granulated with an aqueous solution of (4). (5) is added to the dried granulated material. From this mixture tablets are pressed, biplanar, faceted on both sides and with a dividing notch on one side.

[1020] Diameter of the tablets: 12 mm.

EXAMPLE V

[1021] Capsules containing 50 mg of active substance

[1022] Composition: (1) Active substance  50.0 mg (2) Dried maize starch  58.0 mg (3) Powdered lactose  50.0 mg (4) Magnesium stearate  2.0 mg 160.0 mg

[1023] Preparation:

[1024] (1) is triturated with (3). This trituration is added to the mixture of (2) and (4) with vigorous mixing.

[1025] This powder mixture is packed into size 3 hard gelatine capsules in a capsule filling machine.

EXAMPLE VI

[1026] Capsules containing 350 mg of active substance

[1027] Composition: (1) Active substance 350.0 mg (2) Dried maize starch  46.0 mg (3) Powdered lactose  30.0 mg (4) Magnesium stearate  4.0 mg 430.0 mg

[1028] Preparation:

[1029] (1) is triturated with (3). This trituration is added to the mixture of (2) and (4) with vigorous mixing.

[1030] This powder mixture is packed into size 0 hard gelatine capsules in a capsule filling machine.

EXAMPLE VII

[1031] Suppositories containing 100 mg of active substance 1 suppository contains: Active substance   100.0 mg Polyethyleneglycol (M.W. 1500)   600.0 mg Polyethyleneglycol (M.W. 6000)   460.0 mg Polyethylenesorbitan monostearate   840.0 mg 2,000.0 mg

[1032] Preparation:

[1033] The polyethyleneglycol is melted together with polyethylenesorbitan monostearate. At 40° C. the ground active substance is homogeneously dispersed in the melt. It is cooled to 38° C. and poured into slightly chilled suppository moulds. 

We claim:
 1. A compound of formula (I)

wherein: R¹ is an amino, C₁₋₃-alkylamino, C₃₋₇-cycloalkylamino, or (phenyl-C₁₋₃-alkyl)-amino group each additionally optionally substituted at the amino nitrogen atom by a phenylcarbonyl or phenylsulfonyl group or by C₁₋₅-alkyl or C₁₋₅-alkylcarbonyl group optionally substituted in the alkyl moiety by a hydroxy, C₁₋₃-alkyloxy, or carboxy group, a group that is converted in vivo into a carboxy group, an amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, or a 4- to 7-membered cycloalkyleneimino group, wherein at the abovementioned substituted C₁₋₅-alkyl group, two heteroatoms are separated from one another by at least two carbon atoms, a 4- to 7-membered cycloalkyleneiminocarbonyl or cycloalkyleneiminosulfonyl group, wherein: the cycloalkyleneimino moiety is optionally substituted in the carbon skeleton by a fluorine, chlorine, or bromine atom, one or two C₁₋₃-alkyl, C₂₋₃-alkenyl, C₂₋₃-alkynyl, hydroxy-C₁₋₃-alkyl, C₁₋₃-alkyloxy-C₁₋₃-alkyl, phenyl-C₁₋₃-alkyl, 1,1-diphenyl-C₁₋₃-alkyl, heteroaryl-C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₃₋₆-cycloalkylamino-C₁₋₃-alkyl, phenylamino-C₁₋₃-alkyl, C₁₋₅-alkylamino-C₁₋₃-alkyl, di-(C₁₋₅-alkyl)-amino-C₁₋₃-alkyl, N—(C₃₋₄-cycloalkyl)-C₁₋₃-alkylamino-C₁₋₃-alkyl, a 4- to 7-membered cycloalkyleneimino-C₁₋₃-alkyl, N—(C₁₋₃-alkylcarbonyl)-C₁₋₃-alkylamino-C₁₋₃-alkyl, carboxy-C₁₋₃-alkyl, C₁₋₃-alkyloxy-carbonyl-C₁₋₃-alkyl, aminocarbonyl-C₁₋₃-alkyl, C₁₋₃-alkylaminocarbonyl-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-aminocarbonyl-C₁₋₃-alkyl, a 4- to 7-membered cycloalkyleneiminocarbonyl-C₁₋₃-alkyl, C₁₋₅-alkyloxycarbonylamino-C₁₋₃-alkyl, C₁₋₃-alkylcarbonylamino-C₁₋₃-alkyl, C₁₋₃-alkylsulfonylamino-C₁₋₃-alkyl, aminocarbonylamino-C₁₋₃-alkyl, C₁₋₃-alkylaminocarbonylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-aminocarbonylamino-C₁₋₃-alkyl, carboxy, C₁₋₃-alkyloxycarbonyl, benzyloxycarbonyl, C₁₋₃-alkylcarbonyl, aminocarbonyl, C₁₋₃-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl, N—(C₃₋₇-cycloalkyl)-C-5-alkylaminocarbonyl, N-(phenyl-C₁₋₃-alkyl)-C₁₋₅-alkylaminocarbonyl, a 4- to 7-membered cycloalkyleneiminocarbonyl, aminocarbonyl-C₁₋₃-alkylaminocarbonyl, hydroxy, C₁₋₃-alkyloxy, allyloxy, propargyloxy, benzyloxy, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, a 4- to 7-membered cycloalkyleneimino, trifluoromethylcarbonylamino, a mono-, di-, or trifluoromethylamino, a phenyl or a 5- to 6-membered heteroaryl group, with the proviso that, in the substitution of a methylene group adjacent to the imino group, two heteroatoms are separated from one another by at least two carbon atoms, and/or a methylene group in the 3 position of a 5-membered cycloalkyleneimino group is optionally replaced by a sulfur atom, or a sulfinyl or sulfonyl group or a methylene group in the 4 position of a 6- or 7-membered cycloalkyleneimino group is optionally replaced by an oxygen or sulfur atom, a carbonyl, sulfinyl, or sulfonyl group or by an —NH— group optionally substituted by a C₁₋₃-alkyl, hydroxy, formyl, or C₁₋₃-alkylcarbonyl group, wherein additionally a methylene group adjacent to the abovementioned optionally substituted —NH— group is optionally replaced by a carbonyl, sulfinyl, or sulfonyl group, with the proviso that in the substitution of the above-mentioned 6- to 7-membered cycloalkyleneimino groups wherein a methylene group is replaced by an oxygen or sulfur atom or a sulfinyl or sulfonyl group, two heteroatoms are separated from one another by at least two carbon atoms, a 5- to 7-membered cycloalkenyleneiminocarbonyl or cycloalkenyleneiminosulfonyl group optionally substituted by one or two C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, a 4- to 7-membered cycloalkyleneimino-C₁₋₃-alkyl, C₃₋₆-cycloalkylamino-C₁₋₃-alkyl, phenyl, phenyl-C₁₋₃-alkyl, heteroaryl, heteroaryl-C₁₋₃-alkyl, aminocarbonyl, C₁₋₃-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl, or 4- to 7-membered cycloalkyleneiminocarbonyl groups, wherein the double bond is not bound to a nitrogen atom and is optionally fused to a 5- or 6-membered heteroaryl group, an aminocarbonyl or aminosulfonyl group optionally substituted by one or two C₁₋₅-alkyl, C₂₋₃-alkenyl, C₂₋₃-alkynyl, C₃₋₆-cycloalkyl, or 5- to 7-membered cycloalkyleneimino groups, wherein the substituents are identical or different, and in each case one of the C₁₋₅-alkyl groups is optionally substituted by one or two hydroxy-C₁₋₃-alkyl, C₁₋₃-alkoxy-C₁₋₃-alkyl, benzyloxy-C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, a 4- to 7-membered cycloalkyleneimino-C₁₋₃-alkyl, C₁₋₅-alkyloxycarbonylamino-C₁₋₃-alkyl, C₃₋₄-cycloalkylamino-C₁₋₃-alkyl, aminocarbonyl, C₁₋₃-alkylaminocarbonyl, N—(C₃₋₇-cycloalkyl)-C₁₋₃-alkylaminocarbonyl, N-(phenyl-C₁₋₃-alkyl)-C₁₋₅-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl, or a 4- to 7-membered cycloalkyleneiminocarbonyl group, a C₁₋₇-alkylcarbonyl or C₃₋₇-cycloalkylcarbonyl group, wherein: the methylene group in the 2, 3, or 4 position in a C₃₋₇-cycloalkylcarbonyl group is optionally replaced by an oxygen or sulfur atom, or a carbonyl, sulfinyl, sulfonyl, or —NH-group, wherein the hydrogen atom of the —NH— group is optionally replaced by a C₁₋₃-alkyl or C₁₋₃-alkylcarbonyl group, a phenylcarbonyl or heteroarylcarbonyl group which is optionally substituted in the phenyl or heteroaryl moiety by a fluorine, chlorine, or bromine atom, or a trifluoromethyl, C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, 4- to 7-membered cycloalkyleneimino-C₁₋₃-alkyl, or C₁₋₃-alkoxy group, a C₁₋₃-alkyl group optionally monosubstituted by an amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, hydroxy, phenyl, heteroaryl, or 4- to 7-membered cycloalkyleneimino group, wherein: the phenyl moiety is optionally substituted by a fluorine, chlorine, or bromine atom, or a trifluoromethyl, C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, 4- to 7-membered cycloalkyleneimino-C₁₋₃-alkyl, or C₁₋₃-alkoxy group, and/or a —CH₂—CH₂— group in a 5- to 7-membered cycloalkyleneimino group is optionally replaced by a —NH—CO—, —CO—NH—, —CO—N(CH₃)—, or —N(CH₃)—CO— group, or a methylene group, which is adjacent to the nitrogen atom, in a 5- to 7-membered cycloalkyleneimino group is optionally replaced by a carbonyl group, or a group of formula:

wherein in the heterocyclic moiety in each case a hydrogen atom is optionally replaced by a C₁₋₃-alkyl, C₁₋₃-alkyloxy, C₁₋₃-alkyloxycarbonyl, C₁₋₅-alkyloxycarbonylamino-C₁₋₃-alkyl, methylsulfonylmethyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, 4- to 7-membered cycloalkyleneimino-C₁₋₃-alkyl, morpholin-4-yl-C₁₋₃-alkyl, piperazinyl-C₁₋₃-alkyl, N-(C₁₋₃-alkyl)piperazin-4-yl-C₁₋₃-alkyl, aminocarbonyl, C₁₋₃-alkylaminocarbonyl, or di-(C₁₋₃-alkyl)-aminocarbonyl group, and m is 1 or 2; R² is a hydrogen, fluorine, chlorine, or bromine atom, or a C₁₋₃-alkyl group wherein the hydrogen atoms are optionally wholly or partly replaced by fluorine atoms, or a C₂₋₃-alkenyl, C₂₋₃-alkynyl, C₁₋₃-alkoxy, or mono-, di-, or trifluoromethoxy groups; R³ is a hydrogen atom or a C₁₋₃-alkyl group; R⁴ is a hydrogen atom, or a C₂₋₃-alkenyl or C₂₋₃-alkynyl group, or a straight-chain or branched C₁₋₅-alkyl group which is optionally substituted by a fluorine atom, or a mono-, di-, or trifluoromethyl, a nitrile, hydroxy, a C₁₋₅-alkyloxy group wherein the hydrogen atoms are optionally wholly or partly replaced by fluorine atoms, an allyloxy, propargyloxy, benzyloxy, C₁₋₅-alkylcarbonyloxy, C₁₋₅-alkyloxycarbonyloxy, carboxy-C₁₋₃-alkyloxy, C₁₋₅-alkyloxycarbonyl-C₁₋₃-alkyloxy, C₁₋₈-alkyloxycarbonylamino, chloro-C₂₋₃-alkylaminocarbonylamino, mercapto, C₁₋₃-alkylsulfanyl, C₁₋₃-alkylsulfinyl, C₁₋₃-alkylsulfonyl, C₁₋₃-alkylcarbonylamino-C₁₋₃-alkylsulfanyl, C₁₋₃-alkylcarbonylamino-C₁₋₃-alkylsulfinyl, C₁₋₃-alkylcarbonylamino-C₁₋₃-alkylsulfonyl, carboxy, C₁₋₃-alkyloxycarbonyl, allyloxycarbonyl, propargyloxycarbonyl, benzyloxycarbonyl, aminocarbonyl, C₁₋₃-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl, aminosulfonyl, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, C₁₋₅-alkylcarbonylamino, C₁₋₃-alkylsulfonylamino, N-(C₁₋₃-alkylsulfonyl)-C₁₋₃-alkylamino, C₃₋₆-cycloalkylcarbonylamino, aminocarbonylamino, C₁₋₃-alkylaminocarbonylamino, di-(C₁₋₃-alkyl)-aminocarbonylamino, a 4- to 7-membered cycloalkyleneiminocarbonylamino, benzyloxycarbonylamino, phenylcarbonylamino, heteroaryl, or guanidino group, a group of formula

 wherein: o is 2, 3, 4, or 5, R¹¹ is a hydrogen atom or a C₁₋₃-alkyl group, and A is a heteroaryl group or a C₅₋₇-cycloalkyl group wherein: the methyne group is optionally replaced in the 1 position by a nitrogen atom, and/or a methylene group is optionally replaced by an oxygen or sulfur atom, or an —NH—, —N(OH)—, —N(C₁₋₃-alkyl)-, —N(C₁₋₃-alkylcarbonyl)-, or —N(heteroaryl)- group, and/or a methylene group adjacent to an —NH—, —N(OH)—, —N(C₁₋₃-alkyl)-, —N(C₁₋₃-alkylcarbonyl)-, or —N(heteroaryl)- group are additionally optionally replaced by a carbonyl, sulfinyl, or sulfonyl group, a 4- to 7-membered cycloalkyleneiminocarbonyl-C₁₋₃-alkyl group, wherein: a methylene group of the cycloalkyleneimino moiety is optionally substituted by a C₁₋₃-alkyl group optionally substituted by a hydroxy, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, 4- to 7-membered cycloalkyleneimino, or C₁₋₅-alkyloxycarbonylamino group, an aminocarbonyl, C₁₋₃-alkylaminocarbonyl, or di-(C₁₋₃-alkyl)-aminocarbonyl group, and a methylene group of the cycloalkyleneimino moiety not adjacent to the imino group is optionally substituted by a hydroxy, amino, C₁₋₃-alkylamino, or di-(C₁₋₃-alkyl)-amino- group, and/or a methylene group in the 4 position of a 6- or 7-membered cycloalkyleneimino group is optionally replaced by an oxygen or sulfur atom, or a carbonyl, sulfinyl, sulfonyl, or —NH-group optionally substituted by a C₁₋₃-alkyl group and additionally a methylene group adjacent to an abovementioned —NH— or —N(C₁₋₃-alkyl) group is optionally replaced by a carbonyl group, or a methylene group in the 2 position of a 5-membered cycloalkyleneimino group is optionally replaced by a carbonyl, sulfinyl, or sulfonyl group, a C₁₋₃-alkyl group which is terminally substituted by a group of formula

 wherein: p in each case is 1 or 2, and R⁸ is a hydrogen atom, or a C₁₋₃-alkyl or C₁₋₃-alkylcarbonyl group, a phenyl or heteroaryl, phenylcarbonyl-C₁₋₃-alkyl, phenyl-C₁₋₃-alkyl, or heteroaryl-C₁₋₃-alkyl group which is optionally mono- or polysubstituted by fluorine, chlorine, or bromine atoms, or C₁₋₃-alkyl, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, hydroxy, C₁₋₄-alkyloxy, mono-, di-, or trifluoromethoxy, benzyloxy, carboxy-C₃-alkyloxy, C₁₋₃-alkyloxycarbonyl-C₁₋₃-alkyloxy, aminocarbonyl-C₁₋₃-alkyloxy, C₁₋₃-alkylaminocarbonyl-C₁₋₃-alkyloxy, di-(C₁₋₃-alkyl)-aminocarbonyl-C₁₋₃-alkyloxy, a 4- to 7-membered cycloalkyleneiminocarbonyl-C₁₋₃-alkoxy, carboxy, or C₁₋₃-alkyloxycarbonyl group, a C₃₋₆-cycloalkyl or a 4- to 7-membered cycloalkyleneimino group optionally substituted by a C₁₋₃-alkylcarbonyl or C₁₋₄-alkyloxycarbonyl group which is bound via a carbon atom, or a 3- to 7-membered cycloalkyl-C₁₋₃-alkyl or cycloalkyleneimino-C₁₋₃-alkyl group wherein in the cyclic moiety a methylene group is optionally replaced by an —NH— group optionally substituted by a C₁₋₃-alkyl or C₁₋₃-alkylcarbonyl group and wherein additionally a methylene group adjacent to an —NH—, —N(C₁₋₃-alkylcarbonyl)-, or —N(C₁₋₃-alkyl)- group is optionally replaced in each case by a carbonyl or sulfonyl group, with the proviso that a cycloalkyleneimino group as hereinbefore defined wherein two nitrogen atoms are separated from one another by precisely one —CH₂— group is excluded, R⁵ is a hydrogen atom or a C₁₋₃-alkyl group, or R⁴ and R⁵ together with the carbon atom to which they are bound, is a C₃₋₇-cycloalkyl group, wherein one of the methylene groups of the C₃₋₇-cycloalkyl group is optionally replaced by an imino, C₁₋₃-alkylimino, acylimino, or sulfonylimino group, A is a carbonylamino or aminocarbonyl group, wherein the hydrogen atom of the amino function is optionally substituted by a C₁₋₃-alkyl group, and B is

 wherein: n is 1 or 2, R⁶ is a hydrogen atom or a C₁₋₃-alkyl, hydroxy, C₁₋₅-alkyloxycarbonyl, carboxy-C₁₋₃-alkyl, C₁₋₃-alkyloxycarbonyl-C₁₋₃-alkyl, amino, or C₁₋₃-alkylamino group and R⁷ is a hydrogen, fluorine, chlorine, or bromine atom, a C₁₋₃-alkyl group wherein the hydrogen atoms is optionally wholly or partly replaced by fluorine atoms, a C₂₋₃-alkenyl or C₂₋₃-alkynyl, a hydroxy, C₁₋₃-alkoxy, trifluoromethoxy, amino, nitro, or cyano group, wherein, unless otherwise stated: (i) “heteroaryl group” means a monocyclic 5- or 6-membered heteroaryl group optionally substituted in the carbon skeleton by a fluorine, chlorine, bromine, or iodine atom, or a C₁₋₃-alkyl, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, C₁₋₃-alkyloxy, carboxy, C₁₋₃-alkoxy-carbonyl, or C₁₋₃-alkoxycarbonylamino group, wherein: the 6-membered heteroaryl group contains one, two, or three nitrogen atoms and the 5-membered heteroaryl group contains an imino group optionally substituted by a C₁₋₃-alkyl or phenyl-C₁₋₃-alkyl group, or an oxygen or sulfur atom, or an imino group optionally substituted by a C₁₋₃-alkyl, amino-C₂₋₃-alkyl, C₁₋₃-alkylamino-C₂₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₂₋₃-alkyl, a 4- to 7-membered cycloalkyleneimino-C₁₋₃-alkyl, or phenyl-C₁₋₃-alkyl group, or an oxygen or sulfur atom and additionally a nitrogen atom or an imino group optionally substituted by a C₁₋₃-alkyl or phenyl-C₁₋₃-alkyl group and two or three nitrogen atoms, and also a phenyl ring optionally substituted by a fluorine, chlorine, or bromine atom, or a C₁₋₃-alkyl, hydroxy or C₁₋₃-alkyloxy group is optionally fused to the above-mentioned monocyclic heteroaryl groups via two adjacent carbon atoms, and the bond is effected via a nitrogen atom or via a carbon atom of the heterocyclic moiety or a fused-on phenyl ring, (ii) the alkyl and alkoxy groups contained in the above definitions which have more than two carbon atoms is straight-chain or branched and the alkyl groups in the above-mentioned dialkylated groups are identical or different, and (iii) the hydrogen atoms of the methyl or ethyl groups contained in the above-mentioned definitions are optionally wholly or partly replaced by fluorine atoms, and the tautomers and the salts thereof.
 2. The compound of formula I according to claim 1, wherein each group which is converted in vivo into a carboxy group is selected from a carboxy group esterified with an alcohol reagent, with the proviso that no bond to the oxygen atom starts from a carbon atom which carries a double or triple bond, a C₃₋₈-cycloalkyl-C₁₋₃-alkanol, or an alcohol of formula: R⁹—CO—O—(R₁₀CR₁₁)—OH, wherein: R⁹ is a C₁₋₈-alkyl, C₅₋₇-cycloalkyl, phenyl, or phenyl-C₁₋₃-alkyl group; R¹⁰ is a hydrogen atom, a C₁₋₃-alkyl, C₅₋₇-cycloalkyl, or phenyl group; and R¹¹ is a hydrogen atom or a C₁₋₃-alkyl group, and the tautomers and the salts thereof.
 3. The compound of formula I according to claim 1, wherein the alcohol reagent is a C₁₋₆-alkanol, a phenyl-C₁₋₃-alkanol, a C₃₋₉-cycloalkanol, a C₅₋₇-cycloalkenol, a C₃₋₅-alkenol, a phenyl-C₃₋₅-alkenol, a C₃₋₅-alkynol, or a phenyl-C₃₋₅-alkynol, and the tautomers and the salts thereof.
 4. The compound of formula I according to claim 1, wherein R³ is a hydrogen atom, and the tautomers and the salts thereof.
 5. A compound of formula Ia

wherein: R¹, R², R⁴, R⁵, and B are as defined in claim 1, wherein R⁴ is not a hydrogen atom, and R⁶ is a hydrogen atom, and the tautomers and the salts thereof.
 6. The compound of formula I according to claim 1, wherein R² is not a hydrogen atom, and B is

and the tautomers and the salts thereof.
 7. The compound of formula I according to claim 5, wherein R² is a hydrogen atom, and the tautomers and the salts thereof.
 8. A compound of formula Ib

wherein R¹, R², R⁴, and R⁵ are as defined in claim 1, wherein R⁴ is not a hydrogen atom, and R⁷ is a fluorine, chlorine, or bromine atom, a C₁₋₃-alkyl group wherein the hydrogen atoms are optionally wholly or partly replaced by fluorine atoms, or a C₂₋₃-alkenyl or C₂₋₃-alkynyl, a C₁₋₃-alkyloxy, trifluoromethoxy, or cyano group, and the tautomers and the salts thereof.
 9. The compound of formula I according to claim 1, wherein: R¹ is an amino, C₁₋₅-alkylamino, C₃₋₇-cycloalkylamino, or (phenyl-C₁₋₃-alkyl)-amino group which is optionally additionally substituted in each case at the amino nitrogen atom by a C₁₋₅-alkyl or C₁₋₅-alkylcarbonyl group optionally substituted in the alkyl moiety by a carboxy group, a group which is converted in vivo into a carboxy group, an amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino or a 4- to 7-membered cycloalkyleneimino group, wherein in the abovementioned substituted C, s-alkyl group, two heteroatoms are separated from one another by at least two carbon atoms, a 4- to 7-membered cycloalkyleneiminocarbonyl or cycloalkyleneiminosulfonyl group, wherein: the cycloalkyleneimino moiety in the carbon skeleton is optionally substituted by one or two C₁₋₃-alkyl, hydroxy-C₁₋₃-alkyl, C₁₋₃-alkyloxy-C₁₋₃-alkyl, phenyl-C₁₋₃-alkyl, heteroaryl-C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₃₋₆-cycloalkylamino-C₁₋₃-alkyl, C₁₋₅-alkylamino-C₁₋₃-alkyl, di-(C₁₋₅-alkyl)-amino-C₁₋₃-alkyl, N—(C₃₋₆-cycloalkyl)-C₁₋₃-alkylamino-C₁₋₃-alkyl, a 4- to 7-membered cycloalkyleneimino-C₁₋₃-alkyl, carboxy-C₁₋₃-alkyl, C₁₋₃-alkyloxycarbonyl-C₁₋₃-alkyl, aminocarbonyl-C₁₋₃-alkyl, C₁₋₃-alkylaminocarbonyl-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-aminocarbonyl-C 13-alkyl, a 4- to 7-membered cycloalkyleneiminocarbonyl-C₁₋₃-alkyl, C₁₋₅-alkyloxycarbonylamino-C₁₋₃-alkyl, C₁₋₃-alkylcarbonylamino-C₁₋₃-alkyl, C₁₋₃-alkylsulfonylamino-C₁₋₃-alkyl, aminocarbonylamino-C₁₋₃-alkyl, C₁₋₃-alkylaminocarbonylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-aminocarbonylamino-C₁₋₃-alkyl, C₁₋₃-alkyloxycarbonyl, aminocarbonyl, C₁₋₃-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, a phenyl, or a 5- to 6-membered heteroaryl group, with the proviso that in the substitution of a methylene group adjacent to the imino group, two heteroatoms are separated from one another by at least two carbon atoms, and/or a methylene group in the 3 position of a 5-membered cycloalkyleneimino group is optionally replaced by a sulfur atom, or a sulfinyl or sulfonyl group or a methylene group in the 4 position of a 6- or 7-membered cycloalkyleneimino group is optionally replaced by an oxygen or sulfur atom, or a carbonyl or by an —NH— group optionally substituted by a methyl or hydroxy group, wherein additionally a methylene group adjacent to the abovementioned —NH— group is optionally replaced by a carbonyl group, a 5- to 7-membered cycloalkenyleneiminocarbonyl group optionally substituted by one or two C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, a 4- to 7-membered cycloalkyleneimino-C₁₋₃-alkyl, or C₃₋₆-cycloalkylamino-C₁₋₃-alkyl groups, wherein the double bond is not bound to a nitrogen atom and is optionally fused to a 5- or 6-membered heteroaryl group, an aminocarbonyl group optionally substituted by one or two C₁₋₅-alkyl, allyl, propargyl, C₃₋₆-cycloalkyl, or 5- to 7-membered cycloalkyleneimino groups, wherein the substituents are identical or different, and in each case one of the C₁₋₅-alkyl groups is optionally substituted by one or two hydroxy-C₁₋₃-alkyl, C₁₋₃-alkoxy-C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, a 4- to 7-membered cycloalkyleneimino-C₁₋₃-alkyl, or C₃₋₆-cycloalkylamino-C₁₋₃-alkyl group, a C₁₋₃-alkyl group optionally monosubstituted by a di-(C₁₋₃-alkyl)-amino, heteroaryl, or a 4- to 7-membered cycloalkyleneimino group, wherein: a —CH₂—CH₂— group in a 5- to 7-membered cycloalkyleneimino group is optionally replaced by a —NH—CO—, —CO—NH—, —CO—N(CH₃)—, or a —N(CH₃)—CO— group or a methylene group, which is adjacent to the nitrogen atom, in a 5- to 7-membered cycloalkyleneimino group is optionally replaced by a carbonyl group, or a group of formula

wherein in the heterocyclic moiety a hydrogen atom is optionally replaced in each case by a C₁₋₃-alkyloxycarbonyl, C₁₋₅-alkyloxycarbonylamino-C₁₋₃-alkyl, amino-C₁₋₃-alkyl, C₁₋₃-alkylamino-C₁₋₃-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₃-alkyl, or aminocarbonyl group, and m is 1 or 2; R² is a fluorine, chlorine, or bromine atom, or a C₁₋₃-alkyl group wherein the hydrogen atoms is optionally wholly or partly replaced by fluorine atoms, a C₂₋₃-alkenyl, C₂₋₃-alkynyl, or C₁₋₃-alkyloxy group wherein the hydrogen atoms is optionally wholly or partly replaced by fluorine atoms; R³ is a hydrogen atom; R⁴ is a hydrogen atom, a C₂₋₃-alkenyl or C₂₋₃-alkynyl group or a straight-chain or branched C₁₋₅-alkyl group which is optionally substituted by a hydroxy, a C₁₋₃-alkyloxy group wherein the hydrogen atoms is optionally wholly or partly replaced by fluorine atoms, an allyloxy, propargyloxy, benzyloxy, carboxy-C₁₋₃-alkyloxy, C₁₋₃-alkyloxycarbonyl-C₁₋₃-alkyloxy, C₁₋₅-alkyloxycarbonylamino, chloro-C₁₋₃-alkylaminocarbonylamino, mercapto, C₁₋₃-alkylsulfanyl, C₁₋₃-alkylsulfinyl, C₁₋₃-alkylsulfonyl, carboxy, C₁₋₃-alkyloxycarbonyl, aminocarbonyl, C₁₋₃-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, a 4- to 7-membered cycloalkyleneimino, C₁₋₅-alkylcarbonylamino, C₃₋₆-cycloalkylcarbonylamino, C₁₋₃-alkylsulfonylamino, benzyloxycarbonylamino or phenylcarbonylamino group, a 4- to 7-membered cycloalkyleneiminocarbonyl-C₁₋₃-alkyl group, wherein: a methylene group of the cycloalkyleneimino moiety is optionally substituted by a C₁₋₃-alkyl group optionally substituted by a hydroxy, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, a 4- to 7-membered cycloalkyleneimino or C₁₋₅-alkyloxycarbonylamino group and a methylene group of the cycloalkyleneimino moiety not adjacent to the imino group is optionally substituted by a hydroxy, amino, C₁₋₃-alkylamino, di-(C₁₋₃-alkyl)-amino, aminocarbonyl, C₁₋₃-alkylaminocarbonyl, or di-(C₁₋₃-alkyl)-aminocarbonyl group, and/or a methylene group in the 4 position of a 6- or 7-membered cycloalkyleneimino group is optionally replaced by an oxygen or sulfur atom, or a carbonyl, sulfinyl, sulfonyl, or —NH-group optionally substituted by a C₁₋₃-alkyl group, and additionally a methylene group adjacent to an abovementioned —NH— or —N(C₁₋₃-alkyl) group is optionally replaced by a carbonyl group, a C₁₋₃-alkyl group which is terminally substituted by a group of formula

 wherein: p is 1 or 2, and R³ is a hydrogen atom, or a C₁₋₃-alkyl or C₁₋₃-alkylcarbonyl group, a phenyl, thiophenyl or pyridinyl, phenyl-C₁₋₃-alkyl, tetrazolyl-C₁₋₃-alkyl, imidazolyl-C₁₋₃-alkyl, thiazolyl-C₁₋₃-alkyl, or thiophenyl-C₁₋₃-alkyl group which is optionally substituted by a chlorine atom, or a hydroxy, C₁₋₄-alkyloxy, trifluoromethoxy, carboxy, or C₁₋₃-alkyloxycarbonyl group, R⁵ is a hydrogen atom, A is a carbonylamino or aminocarbonyl group, and B is

 wherein: R⁷ is a fluorine, chlorine, or bromine atom, and the tautomers and the salts thereof.
 10. A compound of formula Ib

wherein R¹, R², R⁴, and R⁵ are as defined in claim 9, wherein R⁴ is not a hydrogen atom, and R⁷ is a chlorine or bromine atom, and the tautomers and the salts thereof.
 11. A compound of formula Ic

wherein: R¹ is a group of formula

 wherein: R¹ ² is a hydrogen atom, or a methyl, aminomethyl, C₁₋₃-alkylamino-C₁₋₂-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₂-alkyl, pyrrolidin-1-ylmethyl, or 2-(pyrrolidin-1-yl)ethyl group, and R¹³ is a hydrogen atom, a methyl or aminomethyl group; R² is a fluorine, chlorine, or bromine atom, or a methyl, ethyl, trifluoromethyl, or methoxy group; R⁴ is a C₁₋₄-alkyl group which may be substituted by a fluorine atom, a hydroxy, C₁₋₃-alkyloxy, trifluoromethoxy, 2,2,2-trifluoroethyloxy, allyloxy, propargyloxy, mercapto, C₁₋₄-alkyl-sulfanyl, C₁₋₄-alkylsulfinyl, C₁₋₄-alkylsulfonyl, amino, C₁₋₃-alkylcarbonylamino, C₁₋₃-alkylsulfonylamino, carboxy, aminocarbonyl, C₁₋₃-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl, or a 4- to 7-membered cycloalkyleneiminocarbonyl group, a phenyl, thiophenyl, phenyl-C₁₋₃-alkyl, tetrazolyl-C₁₋₃-alkyl, imidazolyl-C₁₋₃-alkyl, thiazolyl-C₁₋₃-alkyl or thiophenyl-C₁₋₃-alkyl group, and R⁷ is a chlorine or bromine atom, and the tautomers and the salts thereof.
 12. The compound of formula Ic according to claim 11, wherein: R¹ is a group of formula

 wherein: R¹² is a hydrogen atom, a methyl, aminomethyl, C₁₋₃-alkylamino-C₁₂-alkyl, di-(C₁₋₃-alkyl)-amino-C₁₋₂-alkyl, pyrrolidin-1-ylmethyl, or 2-(pyrrolidin-1-yl)ethyl group and R¹³ is a hydrogen atom, a methyl, or aminomethyl group; R² is a fluorine, chlorine, or bromine atom, or a methyl, ethyl, trifluoromethyl, or methoxy group; R⁴ is a C₁₋₄-alkyl group which is substituted by a fluorine atom, or a hydroxy, C₁₋₃-alkyloxy, trifluoromethoxy, 2,2,2-trifluoroethyloxy, allyloxy, propargyloxy, mercapto, C₁₋₄-alkyl-sulfanyl, C₁₋₄-alkylsulfinyl, C₁₋₄-alkylsulfonyl, amino, C₁₋₃-alkylcarbonylamino, C₁₋₃-alkylsulfonylamino, carboxy, aminocarbonyl, C₁₋₃-alkylaminocarbonyl, di-(C₁₋₃-alkyl)-aminocarbonyl or a 4- to 7-membered cycloalkyleneiminocarbonyl group, a phenyl, thiophenyl, phenyl-C₁₋₃-alkyl, tetrazolyl-C₁₋₃-alkyl, imidazolyl-C₁₋₃-alkyl, thiazolyl-C₁₋₃-alkyl, or thiophenyl-C₁₋₃-alkyl group; and R⁷ is a chlorine or bromine atom, the tautomers and the salts thereof.
 13. A compound of formula I according to claim 1, wherein: R¹ is a 2,5-dihydro-1H-pyrrol-1-ylcarbonyl, pyrrolidin-1-ylcarbonyl, N-acetyl-N-cyclobutylamino, 2-(N-tert-butoxycarbonylaminomethyl)pyrrolidin-1-yl-carbonyl, 2-(aminomethyl)pyrrolidin-1-ylcarbonyl, 3-oxopiperazin-1-ylcarbonyl, 4-methyl-3-oxopiperazin-1-ylcarbonyl, 2,3-dihydroimidazo[2,1-b]-thiazol-5-yl, thiazolidin-3-yl-carbonyl, 1,2,3,6-tetrahydropyridin-1-ylcarbonyl, 2-methylthiomorpholin-4-yl-carbonyl, thiomorpholin-4-ylcarbonyl, N-isopropyl-N-methylaminocarbonyl, 2-methoxy-methylpyrrolidin-1-ylcarbonyl, 3-(pyrrolidin-1-ylmethyl)piperidin-1-ylcarbonyl, azetidin-1-ylcarbonyl, 2-methylpyrrolidin-1-ylcarbonyl, N-isobutyl-N-methylaminocarbonyl, [1,4]oxazepan-1-ylcarbonyl, 2,5-dimethylpyrrolidin-1-ylcarbonyl, piperidin-1-yl-carbonyl, 4-hydroxypiperidin-1-ylcarbonyl, 4-acetylpiperazin-1-ylcarbonyl, N,N-diethylaminocarbonyl, 3-methylpiperidin-1-ylcarbonyl, 4-methylpiperidin-1-yl-carbonyl, 2-aminomethylpiperidin-1-ylcarbonyl, 3-aminomethylpiperidin-1-yl-carbonyl, 3-(2-aminoethyl)piperidin-1-ylcarbonyl, 3-aminopiperidin-1-yl-carbonyl, N-(2-dimethylamino)ethyl-N-ethylaminocarbonyl, 2-(N-tert-butoxycarbonylamino-ethyl]pyrrolidin-1-ylcarbonyl, 2-(aminoethyl)pyrrolidin-1-ylcarbonyl, 2-(aminocarbonyl)pyrrolidin-1-ylcarbonyl, 1-oxothiazolidin-3-ylcarbonyl, 1,1-dioxothiazolidin-3-yl-carbonyl, 2-ethoxycarbonylmethyl-3-oxopiperazin-1-ylcarbonyl, 2-dimethylaminocarbonylmethyl-3-oxopiperazin-1-ylcarbonyl, 2-aminomethyl-3-oxopiperazin-1-ylcarbonyl, (2-acetylaminoethyl)pyrrolidin-1-ylcarbonyl, dimethylaminocarbonyl, 2-hydroxymethylpyrrolidin-1-ylcarbonyl, 2-(methylsulfonylaminomethyl)pyrrolidin-1-ylcarbonyl, 2-(acetylaminomethyl)pyrrolidin-1-ylcarbonyl, pyrrolidin-1-ylsulfonyl, 2-(2-ethoxycarbonylethyl)pyrrolidin-1-ylcarbonyl, 2-[(3-ethyl-ureido)methyl]pyrrolidin-1-ylcarbonyl, 4,5,6,7-tetrahydrobenzimidazol-1-yl, 3-(ethoxycarbonyl)-5,6-dihydro-4H-cyclopentapyrazol-1-yl, 3-(tert-butoxycarbonylamino)methyl-5,6-dihydro-4H-cyclopentapyrazol-1-yl, 3-(aminocarbonyl)-5,6-dihydro-4H-cyclopentapyrazol-1-yl, 3-aminomethyl-5,6-dihydro-4H-cyclopentapyrazol-1-yl, 4-formylpiperazin-1-ylcarbonyl, N-ethyl-N-(piperidin-4-yl)aminocarbonyl, 2-(2-dimethylaminoethyl)piperidin-1-ylcarbonyl, 2-(piperidin-1-ylmethyl)piperidin-1-ylcarbonyl, 2-(3-diethylaminopropyl)piperidin-1-yl-carbonyl, 2-(N-butyl-N-ethylaminomethyl)piperidin-1-ylcarbonyl, 2-(N-cyclohexyl-N-methylaminomethyl)piperidin-1-ylcarbonyl, 1,4,6,7-tetrahydroimidazo[4,5-c]pyridin-5-ylcarbonyl, 6,7-dihydro-4H-thieno[3,2-c]pyridin-5-ylcarbonyl, 2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-ylcarbonyl, 2-(ethoxycarbonyl)pyrrolidin-1-ylcarbonyl, 4-hydroxypiperazin-1-ylcarbonyl, 2-(methyloxycarbonyl)pyrrolidin-1-ylcarbonyl, 2-(benzyloxycarbonyl)pyrrolidin-1-ylcarbonyl, 3,4,5,6-tetrahydro-2H-[2,3]-bipyridinyl-1-ylcarbonyl, N-(2-aminoethyl)-N-ethylaminocarbonyl, N-(3-aminopropyl)-N-ethyl-aminocarbonyl, N-cyclopropyl-N-methylaminocarbonyl, 1,4,6,7-tetrahydropyrazol-[4,3-c]pyridin-5-ylcarbonyl, 2-(pyridin-2-yl)pyrrolidin-1-ylcarbonyl, 2-(pyridin-4-yl)pyrrolidin-1-ylcarbonyl, 2,5-dimethyl-2,5-dihydropyrrol-1-ylcarbonyl, 2,5-dimethyl-2,5-dihydropyrrol-1-ylcarbonyl, 2-phenylaminomethylpyrrolidin-1-ylcarbonyl, 2-benzylpyrrolidin-1-ylcarbonyl, 2-phenethylpyrrolidin-1-ylcarbonyl, 2-isopropylpyrrolidin-1-ylcarbonyl, 2-methylpiperidin-1-ylcarbonyl, 4-oxopiperidin-1-ylcarbonyl, [1,4]-diazepan-1-ylcarbonyl, 2-(dimethylaminocarbonyl)pyrrolidin-1-ylcarbonyl, 2-(methylaminocarbonyl)pyrrolidin-1-ylcarbonyl, 2-(aminocarbonylmethylanminocarbonyl)pyrrolidin-1-ylcarbonyl, 2-benzhydrylpyrrolidin-1-ylcarbonyl, 3-(2,2,2-trifluoroacetylamino)pyrrolidin-1-ylcarbonyl, 3-dimethylaminopyrrolidin-1-ylcarbonyl, imidazol-1-ylmethyl, 2-oxopyrrolidin-1-ylmethyl, 3-oxopiperazin-1-ylmethyl, 2-(ethoxycarbonylmethyl)pyrrolidin-1-ylcarbonyl, 2-dimethylaminomethylpyrrolidin-1-ylcarbonyl, 2-(carboxymethyl)pyrrolidin-1-ylcarbonyl, 2-(carboxyethyl)pyrrolidin-1-ylcarbonyl, pyrrol-1-ylcarbonyl, 2-methylpyrrolidin-1-yl-carbonyl, 2-(tert-butoxycarbonylaminomethyl)thiazolidin-3-ylcarbonyl, 2-aminomethylthiazolidin-3-ylcarbonyl, N-ethyl-N-(6-methoxy-hexanoyl)amino, 3-fluoropyrrolidin-1-yl-carbonyl, 2-methylaminocarbonylethylpyrrolidin-1-yl, N-acetyl-N-cyclopentylamino, 2-methyl-aminocarbonylmethylpyrrolidin-1-yl, 2-(imidazol-1-ylmethyl)pyrrolidin-1-ylcarbonyl, 2-[(N-acetyl-N-methylamino)methyl]pyrrolidin-1-ylcarbonyl, benzoyl, 3-methyl-5,6-dihydro-4H-cyclopentapyrazol-1-yl, 4-oxo-4,5,6,7-tetrahydroindol-1-yl, 4,5,6,7-tetrahydroindol-1-yl, 4,5,6,7-tetrahydroindazol-1-yl, 4-oxo-2-propyl-4,5-dihydroimidazo[4,5-c]pyridin-1-yl, 2-methyl-5,6-dihydro-4H-cyclopentaimidazol-1-yl, 2-methyl-4,5,6,7-tetrahydrobenzimidazol-1-yl, 2-hydroxycarbonylmethyl-3-oxopiperazin-1-ylcarbonyl, 4-methoxyimidazo[4,5-c]pyridin-1-yl, 2-carboxypyrrolidin-1-ylcarbonyl, 2-dimethylaminomethylbenzimidazol-1-yl, 4-oxo-4,5-dihydroimidazo[4,5-c]pyridin-1-yl, 2-dimethylaminomethyl-indol-1-yl, 4-oxo-4,5-dihydropyrrol-[3,2-c]pyridin-1-yl, 3-oxo-[1,4]diazepan-1-ylcarbonyl, 2-(pyrrolidin-1-yl)methyl-5,6-dihydro-4H-cyclopentaimidazol-1-yl, 2-(2-(pyrrolidin-1-yl)ethyl)-5,6-dihydro-4H-cyclopentaimidazol-1-yl, 2-(pyrrolidin-1-yl)methyl-4,5,6,7-tetrahydrobenzimidazol-1-yl, 2-(2-pyrrolidin-1-ylethyl)4,5,6,7-tetrahydrobenzimidazol-1-yl, 2-(morpholin-4-yl)methyl-5,6-dihydro-4H-cyclopentaimidazol-1-yl, 2-(2-(morpholin-4-yl)ethyl)-5,6-dihydro-4H-cyclopentaimidazol-1-yl, 2-(morpholin-4-yl)methyl-4,5,6,7-tetrahydrobenzimidazol-1-yl, 2-(2-(morpholin-4-yl)ethyl)-4,5,6,7-tetrahydrobenzimidazol-1-yl, 2-oxohexahydrocyclopentaimidazol-1-yl, 4-oxo-4,5,6,7-tetrahydropyrrol[3,2-c]pyridin-1-yl, 4-oxooctahydropyrrol[3,2-c]pyridin-1-yl, octahydrocyclopentapyrazin-1-yl, 2,3-dioxooctahydrocyclopentapyrazin-1-yl, 2-oxo-2,5,6,7-tetrahydrocyclopentapyrazin-1-yl, 5,6,7,7a-tetrahydro-1H-pyrrol-[1,2-c]-imidazol-3-yl, or 3,4,4a,5,6,7-hexahydropyrrol-[1,2-c]pyrimidin-1-yl group; R² is a fluorine, chlorine, or bromine atom, or a C₁₋₃-alkyl group wherein the hydrogen atoms are optionally wholly or partly replaced by fluorine atoms, or a C₁₋₃-alkyloxy or a C₂₋₃-alkynyl group; R³ is a hydrogen atom; R⁴ is a hydrogen atom or a methyl, ethyl, propyl, isopropyl, isobutyl, tert-butyl, hydroxymethyl, 1-hydroxyethyl, methoxymethyl, 2-methoxyethyl, phenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, benzyl, 4-hydroxybenzyl, 4-methoxy-carbonylmethoxyphenylmethyl, pyridin-4-ylmethyl, pyridin-2-ylmethyl, piperidin-1-yl-methyl, piperidin-3-ylmethyl, 1H-imidazol-4-ylmethyl, aminocarbonylmethyl, 4-benzyloxycarbonylaminobutyl, 2-methylsulfanylethyl, 2-methylsulfinylethyl, 2-methylsulfonylethyl, ethylsulfanylmethyl, ethylsulfinylmethyl, ethylsulfonylmethyl, aminomethyl, 2-aminoethyl, 3-aminopropyl, 4-aminobutyl, 2-phenylethyl, acetylaminomethyl, methylsulfonylaminomethyl, phenylcarbonylaminomethyl, 3-acetylaminopropyl, 4-acetylaminobutyl, 2,2,2-trifluoroethyl, hydroxymethyl, tert-butoxycarbonylaminomethyl, 3-(tert-butoxycarbonylamino)propyl, 4-hydroxybenzyl, 2-carboxyethyl, 2-(benzyloxycarbonyl)ethyl, 2-(ethylaminocarbonyl)ethyl, 2-(pyrrolidin-1-ylcarbonyl)ethyl, 2-(diethylaminocarbonyl)ethyl, tetrazol-2-ylmethyl, carboxymethyloxymethyl, tert-butoxycarbonylmethyloxymethyl, 2-(benzyloxycarbonylamino)ethyl, 2-(aminosulfonyl)ethyl, 2-(2-oxoimidazolidin-1-yl)ethyl, 2-(2-chloroethyl)ureido]ethyl, 1-methoxy-1-methylethyl, 1-(3-tert-butoxycarbonyl)piperidin-3-yl, 1-acetylpiperidin-3-yl, 2-(pyridin-4-yl)ethyl, 2-[3-(dimethylamino)pyrrolidin-1-ylcarbonyl]ethyl, 2-(3-hydroxypyrrolidin-1-yl)carbonylethyl, 2-[2-(hydroxymethyl)pyrrolidin-1-ylcarbonyl]ethyl, 2-(2-methyl-2,6-diazaspiro[3.4]oct-6-ylcarbonyl)ethyl, 2-[2-(aminocarbonyl)pyrrolidin-1-ylcarbonyl)ethyl, 2-[2-(tert-butoxy-carbonylaminomethyl)pyrrolidin-1-ylcarbonyl]ethyl, 2-[3-(hydroxymethylpyrrolidin-1-yl)carbonyl]ethyl, 2-(11,1-dioxo-1-thiomorpholin-4-ylcarbonyl)ethyl, 2-(4-methyl-3-oxopiperazin-1-ylcarbonyl)ethyl, 2-(2-aminomethylpyrrolidin-1-ylcarbonyl)ethyl, isopropoxycarbonyloxymethyl, 2-(2-isopropylaminothiazol-4-yl)ethyl, 2-(5-chloro-1H-benzimidazol-2-yl)ethyl, 5-chloro-1H-benzimidazol-2-yl, thiophen-3-yl, 2-methylsulfonylaminoethyl, benzyloxymethyl, methylsulfanylmethyl, 2-(1,1-dioxoisothiazolidin-2-yl)ethyl, ethoxymethyl, 1-methoxyethyl, allyloxymethyl, 1-tert-butyloxyethyl, 1-hydroxyethyl, prop-2-ynyloxymethyl, 2-(1H-tetrazol-5-yl)ethyl, 1-prop-2-ynyl, 4-[(5-oxopyrrolidin-3-yl)carbonylamino]butyl, 4-[(pyridin-3-yl-)carbonylamino]butyl, 4-[(5-oxopyrrolidin-2-yl)carbonylamino]butyl, 4-[(pyridin-4-yl)carbonylamino]butyl, 4-(1-methylpyrrolidin-2-ylcarbonylamino)butyl, prop-2-enyl, acetylaminomethylsulfanylmethyl, 2-aminocarbonylethyl, 1H-indol-3-yl)methyl, 4-hydroxy-3,5-dimethylphenylmethyl, methoxycarbonylmethyl, 4-hydroxy-2,6-dimethylphenylmethyl, 4-difluoromethoxyphenylmethyl, 3-bromophenylmethyl, 4-trifluoromethylphenylmethyl, 4-ureidobutyl, 3-ureidopropyl, 4-amino-3,5-dibromophenylcarbonylmethyl, allyloxycarbonylmethyl, 3,4-dimethoxyphenylmethyl, thiazol-4-ylmethyl, 3,5-difluorophenylmethyl, 4-fluorophenylmethyl, mercaptomethyl, 1-methyl-1H-imidazol-5-ylmethyl, 1H-benzimidazol-5-ylmethyl, cyclopropylmethyl, 2,2,2-tri-fluoroethyloxymethyl, trifluoromethoxymethyl, difluoromethoxymethyl, or monofluoromethoxymethyl group; R⁵ is a hydrogen atom; A is an aminocarbonyl or carbonylamino group; and B is

 wherein R⁷ is a fluorine, chlorine, or bromine atom or a methyl group, and the tautomers and the salts thereof.
 14. A compound selected from: (1) N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (2) N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (3) N-(5-chloro-1H-benzimidazol-2-yl)methyl-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (4) N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-phenylethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (5) N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-phenylethyl]-3-methyl-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (6) N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-ethynyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (7) N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-ethyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (8) N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(N-cyclobutyl-N-acetylamino)benzamide, (9) N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-chloro-4-[2-(N-tert-butoxycarbonylaminomethyl)pyrrolidin-1-ylcarbonyl]benzamide, (10) (S)-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-4-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (11) (S)-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (12) N-[1-(5-fluoro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (13) N-[1-(5-cyano-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (14) N-[1-(5-methoxy-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (15) (S)-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(1H-imidazol-4-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (16) (R)- and (S)-4-(2-aminomethylpyrrolidin-1-ylcarbonyl)-3-chloro-N-[(1S)-1-(5-chloro-1H-benzimindazol-2-yl)-2-(pyridin-4-yl)ethyl]benzamide, (17) N-[1-(5-chloro-H-benzimidazol-2-yl)ethyl]-3-chloro-4-(2-aminomethylpyrrolidin-1-ylcarbonyl)benzamide, (18) 1-[N-(5-methyl-1H-benzimidazol-2-yl)]ethyl-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (19) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)4-(3-oxopiperazin-1-ylcarbonyl)benzamide, (20) 3-chloro-N-(5-chloro-1H-benzidazol-2-ylmethyl)4-(4-methyl-3-oxo-piperazin-I ylcarbonyl)benzamide, (21) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)4-(2-aminomethylpyrrolidin-1-ylcarbonyl)benzamide, (22) N-(5-chloro-1H-benzimidazol-2-ylmethyl)4-(2,3-dihydroimidazo[2,1-b]thiazol-5-yl)benzamide, (23) 2-(5-chloro-1H-benzimidazol-2-yl)-N-[3-methyl-4-(pyrrolidin-1-ylcarbonyl)phenyl]acetamide, (24) 3-methyl-4-(pyrrolidine-1-carbonyl)-N-[1-(5-trifluoromethyl-1H-benzimidazol-2-yl)ethyl]benzamide, (25) (S)-N-[2-aminocarbonyl-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (26) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (27) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)4-(thiazolidin-3-ylcarbonyl)benzamide (28) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)4-(1,2,3,6-tetrahydropyridin-1-ylcarbonyl)benzamide, (29) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)4-(2-methylthiomorpholine-4-ylcarbonyl)benzamide, (30) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)4-(thiomorpholine-4-ylcarbonyl)benzamide, (31) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)-4-(N-isopropyl-N-methylamino-carbonyl)benzamide, (32) (R)-3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)4-(2-methoxymethylpyrrolidin-1-ylcarbonyl)benzamide, (33) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)4-[3-(pyrrolidin-1-ylmethyl)piperidin-1-ylcarbonyl]benzamide, (34) (S)-3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)4-(2-methoxymethylpyrrolidin-1-ylcarbonyl)benzamide, (35) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)4-(azetidin-1-ylcarbonyl)benzamide, (36) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)-4-(2-methylpyrrolidin-1-ylcarbonyl)benzamide, (37) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)-4-(N-isobutyl-N-methylamino-carbonyl)benzamide, (38) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)4-([1,4]oxazepan-1-ylcarbonyl)benzamide, (39) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)4-(2,5-dimethylpyrrolidin-1-ylcarbonyl)benzamide, (40) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)4-(piperidin-1-ylcarbonyl)benzamide, (41) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)4-(4-hydroxypiperidin-1-ylcarbonyl)benzamide, (42) 4-(4-acetylpiperazin-1-ylcarbonyl)-3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)benzamide, (43) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)4-(pyrrolidin-1-ylcarbonyl)benzamide, (44) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)-4-(N,N-diethylaminocarbonyl)benzamide, (45) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)-4-(3-methylpiperidin-1-ylcarbonyl)benzamide, (46) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)-4-(4-methylpiperidin-1-ylcarbonyl)benzamide, (47) 4-(2-aminomethylpiperidin-1-ylcarbonyl)-3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)benzamide, (48) 4-(3-aminomethylpiperidin-1-ylcarbonyl)-3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)benzamide, (49) 4-[3-(2-aminoethyl)piperidin-1-ylcarbonyl]-3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)benzamide, (50) 4-(2-aminomethylpyrrolidin-1-ylcarbonyl)-3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)benzamide, (51) 4-(3-aminopiperidin-1-ylcarbonyl)-3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)benzamide, (52) N-(6-chloroquinolin-2-ylmethyl)-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (53) N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-N-ethyl-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (54) N-(6-bromo-3H-imidazo[4,5-b]pyridin-2-yl)methyl-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (55) N-(6-bromo-3H-imidazo[4,5-b]pyridin-2-yl)methyl-3-methyl-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (56) N-[1-(5-bromo-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (57) N-[(5-chloro-1H-benzimidazol-2-yl)phenylmethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (58) N-[1-(1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (59) N-[1-(5-chloro-1H-benzimidazol-2-yl)-5-benzyloxycarbonylaminopentyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (60) N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-chloro-4-(3-oxopiperazin-1-ylcarbonyl)benzamide, (61) N-[1-(5-chloro-1H-benzimidazol-2-yl)-3-methylbutyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (62) N-[1-(5-chloro-1H-benzimidazol-2-yl)]ethyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (63) (S)-N-[1-(5-chloro-1H-benzimidazol-2-yl)]ethyl-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (64) N-[1-(5-chloro-H-benzimidazol-2-yl)]ethyl-3-chloro-4-[N-(2-dimethylamino)ethyl-N-ethyl-aminocarbonyl]benzamide, (65) N-[1-(5-chloro-1H-benzimidazol-2-yl)]ethyl-3-bromo-4-(pyrrolidin-1-ylcarbonyl)benzamide, (66) N-[1-(5-chloro-1H-benzimidazol-2-yl)]ethyl-3-trifluoromethyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (67) 4-(2-aminomethylpyrrolidin-1-ylcarbonyl)-N-[2-aminocarbonyl-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-chloro-benzamide, (68) 4-(2-aminomethylpyrrolidin-1-ylcarbonyl)-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(1H-imidazol-4-yl)ethyl]benzamide, (69) 4-(2-aminomethylpyrrolidin-1-ylcarbonyl)-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-2-yl)ethyl]benzamide, (70) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-[(2R/S)-2-(N-tert-butoxycarbonylaminomethyl)pyrrolidin-1-ylcarbonyl]benzamide, (71) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-[(2R/S)-2-amino-methylpyrrolidin-1-ylcarbonyl]benzamide, (72) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-chloro-4-[(2R/S)-2-(N-tert-butoxycarbonylaminomethyl)pyrrolidin-1-ylcarbonyl]benzamide, (73) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-chloro-4-[(2R/S)-2-aminomethylpyrrolidin-1-ylcarbonyl)benzamide, (74) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-chloro-4-[(2S)-2-(N-tert-butoxy-carbonylaminomethyl)pyrrolidin-1-ylcarbonyl]benzamide, (75) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-chloro-4-[(2R)-2-(N-tert-butoxy-carbonylaminomethyl)pyrrolidin-1-ylcarbonyl]benzamide, (76) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-chloro-4-{(2S)-2-[2-(N-tert-butoxycarbonylamino)ethyl]pyrrolidin-1-ylcarbonyl} benzamide, (77) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-chloro-4-[(2S)-2-aminomethylpyrrolidin-1-ylcarbonyl]benzamide, (78) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-chloro-4-[(2R)-2-aminomethylpyrrolidin-1-ylcarbonyl]benzamide, (79) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-chloro-4-[(2S)-2-(2-aminoethyl)pyrrolidin-1-ylcarbonyl]benzamide, (80) N-[(1R/S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-chloro-4-[(2S)-2-amino-carbonylpyrrolidin-1-ylcarbonyl]benzamide, (81) N-[(1R/S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-chloro-4-[(2R)-2-amino-carbonylpyrrolidin-1-ylcarbonyl]benzamide, (82) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)butyl]-3-chloro-4-[(2S)-2-(N-tert-butoxy-carbonylaminomethyl)pyrrolidin-1-ylcarbonyl]benzamide, (83) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfanylpropyl]-3-chloro-4-[(2S)-2-(N-tert-butoxycarbonylaminomethyl)pyrrolidin-1-ylcarbonyl]benzamide, (84) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)butyl]-3-chloro-4-[(2S)-2-aminomethylpyrrolidin-1-ylcarbonyl]benzamide, (85) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfinylpropyl]-3-chloro-4-[(2S)-2-(N-tert-butoxycarbonylaminomethyl)pyrrolidin-1-ylcarbonyl]benzamide, (86) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfonylpropyl]-3-chloro-4-[(2S)-2-(N-tert-butoxycarbonylaminomethyl)pyrrolidin-1-ylcarbonyl]benzamide, (87) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfanylpropyl]-3-chloro-4-[(2S)-2-aminomethylpyrrolidin-1-ylcarbonyl]benzamide, (88) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfinylpropyl]-3-chloro-4-[(2S)-2-aminomethylpyrrolidin-1-ylcarbonyl]benzamide, (89) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfonylpropyl]-3-chloro-4-[(2S)-2-aminomethylpyrrolidin-1-ylcarbonyl]benzamide, (90) rac.-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(thiazolidin-3-ylcarbonyl)benzamide, (91) rac.-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(1-oxothiazolidin-3-ylcarbonyl)benzamide, (92) rac.-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(1,1-dioxothiazolidin-3-ylcarbonyl)benzamide, (93) N-[(1S)-5-(benzyloxycarbonylamino)-1-(5-chloro-1H-benzimidazol-2-yl)pentyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (94) N-[(1S)-5-amino-1-(5-chloro-1H-benzimidazol-2-yl)pentyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (95) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-phenylpropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (96) N-[(1S)-5-acetylamino-1-(5-chloro-1H-benzimidazol-2-yl)pentyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (97) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfanylpropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (98) rac.-N-[-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-chloro-4-(pyrrolidin-1-ylcarbonyl)benzamide, (99) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-3,3,3-trifluoropropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (100) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-hydroxyethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (101) rac.-N-[2-tert-butoxycarbonylamino-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (102) rac.-N-[2-amino-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (103) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(4-hydroxyphenyl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (104) rac.-N-[2-acetylamino-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (105) rac.-N-[2-benzoylamino-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (106) N-[1-(5-chloro-1H-benzimidazol-2-yl)-1-methylethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (107) N-[1-(5-chloro-1H-benzimidazol-2-yl)cyclopropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (108) N-[1-(5-chloro-1H-benzimidazol-2-yl)cyclohexyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (109) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-3-hydroxycarbonylpropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (110) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-hydroxycarbonylpropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (111) rac.-N-[3-benzyloxycarbonyl-1-(5-chloro-1H-benzimidazol-2-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (112) N-[(1S)-3-benzyloxycarbonyl-1-(5-chloro-1H-benzimidazol-2-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (113) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-3-ethylaminocarbonylpropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (114) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-3-(pyrrolidin-1-ylcarbonyl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (115) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-(pyrrolidin-1-ylcarbonyl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (116) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-3-diethylaminocarbonylpropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (117) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-tetrazol-2-ylethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (118) N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-hydroxyethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (119) N-[(1S)-4-(tert-butoxycarbonylamino)-1-(5-chloro-1H-benzimidazol-2-yl)butyl]-3-methyl-4-(pyrrolidine-1-carbonyl)benzamide, (120) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(piperdin-1-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (121) N-[(1R,2R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-hydroxypropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (122) N-[(5-chloro-1H-benzimidazol-2-yl)cyclobutyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (123) N-[(1S)₄-amino-1-(5-chloro-1H-benzimidazol-2-yl)butyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (124) N-[(1S)-2-acetylamino-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (125) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-methylsulfonylaminoethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (126) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-methoxyethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (127) 3-bromo-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-ethyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (128) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methoxypropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (129) N-[(11 S)₄-acetylamino-1-(5-chloro-1H-benzimidazol-2-yl)butyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (130) rac.-N-[(5-chloro-1H-benzimidazol-2-yl)-(3-chlorophenyl)methyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (131) N-[(1R)-2-(C-tert-butoxycarbonylmethyloxy)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (132) N-[(1R)-2-(hydroxycarbonylmethyloxy)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (133) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)4-(3-oxopiperazin-1-ylcarbonyl)benzamide, (134) rac.-4-(2-aminomethylpyrrolidin-1-ylcarbonyl)-3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)benzamide, (135) 3-chloro-N-(5-chloro-1H-benzimidazol-2-ylmethyl)4-(4-methyl-3-oxopiperazin-1-ylcarbonyl)benzamide, (136) 3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(2-ethoxycarbonylmethyl-3-oxopiperazin-1-ylcarbonyl)benzamide, (137) 3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(2-dimethylaminocarbonyl-methyl-3-oxopiperazin-1-ylcarbonyl)benzamide, (138) 4-(2-aminomethyl-3-oxopiperazin-1-ylcarbonyl)-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]benzamide, (139) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(3-oxopiperazin-1-ylcarbonyl)benzamide, (140) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfinylpropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (141) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfonylpropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (142) rac.-N-[(5-chloro-1H-benzimidazol-2-yl)phenylmethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (143) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)phenylmethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-methylbenzamide, (144) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (145) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-methylpropyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-methylbenzamide, (146) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-methylpropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (147) 4-[(2S)-2-(2-acetylaminoethyl)pyrrolidin-1-ylcarbonyl]-3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]benzamide, (148) N-[(1s)-3-(benzyloxycarbonylamino)-1-(5-chloro-1H-benzimidazol-2-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (149) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2,2-dimethylpropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (150) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(dimethylaminocarbonyl)benzamide, (151) N-[(1S)-3-amino-1-(5-chloro-1H-benzimidazol-2-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (152) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-fluoro-4-(pyrrolidin-1-ylcarbonyl)benzamide, (153) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfonylaminopropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (154) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-(2-oxoimidazolidin-1-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (155) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[3-(2-chloroethyl)ureido]propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (156) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-methoxy-2-methylpropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (157) 3-chloro-N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-ethylsulfanylethyl]4-(pyrrolidin-1-ylcarbonyl)benzamide, (158) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)butyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (159) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methoxy-4-(pyrrolidin-1-ylcarbonyl)benzamide, (160) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-hydroxypropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (161) 3-bromo-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfanylpropyl]4-(pyrrolidin-1-ylcarbonyl)benzamide, (162) 3-chloro-N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-(ethylsulfinyl)ethyl]-4-(pyrrolidin-1-ylcarbonyl)benzamide, (163) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-(methylsulfanyl)propyl]-4-(pyrrolidin-1-ylcarbonyl)benzamide, (164) 3-chloro-N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-(ethylsulfonyl)ethyl]-4-(pyrrolidin-1-ylcarbonyl)benzamide, (165) 3-bromo-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-(methylsulfonyl)propyl]-4-(pyrrolidin-1-ylcarbonyl)benzamide, (166) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[(2R)-2-hydroxymethylpyrrolidin-1-ylcarbonyl]benzamide, (167) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[(2S)-2-hydroxymethylpyrrolidin-1-ylcarbonyl]benzamide, (168) N-{(1H-benzimidazol-2-yl)-[1-(3-tert-butoxycarbonyl)piperidin-3-yl]methyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (169) N-{[1-(3-tert-butoxycarbonyl)piperidin-3-yl]-(5-chloro-1H-benzimidazol-2-yl)methyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (170) 3-bromo-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfinylpropyl]-4-(pyrrolidin-1-ylcarbonyl)benzamide, (171) N-[(5-chloro-1H-benzimidazol-2-yl)-(piperidin-3-yl)methyl]-3-methyl-4-(pyrrolidin 1-ylcarbonyl)benzamide, (172) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[(2R,S)-(2-methylpyrrolidin-1-ylcarbonyl)]benzamide, (173) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[(2R)-2-(methyl-sulfonylaminomethyl)pyrrolidin-1-ylcarbonyl]benzamide, (174) 4-[(2R)-2-(acetylaminomethyl)pyrrolidin-1-ylcarbonyl]-3-chloro-N-[(1S)-1-(5-chloro-1-H-benzimidazol-2-yl)ethyl]benzamide, (175) N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (176) (1R)-3-bromo-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-hydroxyethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (177) (1R)-3-methyl-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-methoxyethyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (178) (1R)-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-hydroxyethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (179) rac.-N-[1-(5-chloro-1H-imidazo[4,5-b]pyridin-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (180) rac.-N-[1-(5-chloro-1-methyl-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (181) rac.-N-[1-(6-chloro-1-methyl-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (182) rac.-N-{1-[6-chloro-1-(methoxycarbonylmethyl)-1H-benzimidazol-2-yl]-2-(4-hydroxyphenyl)ethyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (183) rac.-N-{1-[6-chloro-1-(methoxycarbonylmethyl)-1H-benzimidazol-2-yl]-2-(4-methoxycarbonylmethoxyphenyl)ethyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (184) rac.-N-{1-[6-chloro-1-(hydroxycarbonylmethyl)-1H-benzimidazol-2-yl]-2-(4-hydroxyphenyl)ethyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (185) N-[(1S)-1-(7-amino-5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (186) 3-methyl-N-[(1S)-1-(5-nitro-1H-benzimidazol-2-yl)ethyl]-4-(pyrrolidin-1-ylcarbonyl)benzamide, (187) 3-methyl-N-[(1S)-1-(5-amino-1H-benzimidazol-2-yl)ethyl]-4-(pyrrolidin-1-ylcarbonyl)benzamide, (188) 3-chloro-N-[(1S)-1-(6-chloro-1H-benzimidazol-2-yl)ethyl]-4-(pyrrolidin-1-ylsulfonyl)benzamide, (189) N-[(1-acetylpiperidin-3-yl)-(5-chloro-1H-benzimidazol-2-yl)methyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (190) N-[(1-acetylpiperidin-3-yl)-(5-chloro-1H-benzimidazol-2-yl)methyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (191) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-(pyridin-4-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (192) N-[(1S)-3-(benzyloxycarbonylamino)-1-(5-chloro-1H-benzimidazol-2-yl)propyl]-3-methyl-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (193) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[(3R,S)-3-dimethylaminopyrrolidin-1-yl]carbonylpropyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (194) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[(3R)-3-hydroxypyrrolidin-1-yl]carbonylpropyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (195) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[(3S)-3-hydroxypyrrolidin-1-ylcarbonyl]propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (196) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[(2R)-2-hydroxymethylpyrrolidin-1-ylcarbonyl]propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (197) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[(2S)-2-hydroxymethylpyrrolidin-1-ylcarbonyl]propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (198) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-(2-methyl-2,6-diazaspiro[3.4]oct-6-ylcarbonyl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (199) N-{(1S)-3-[(1S)-2-(aminocarbonyl)pyrrolidin-1-ylcarbonyl]-1-(5-chloro-1H-benzimidazol-2-yl)propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (200) N-{(1S)-3-[(1R)-2-(aminocarbonyl)pyrrolidin-1-ylcarbonyl]-1-(5-chloro-1H-benzimidazol-2-yl)propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (201) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[(2S)-2-tert-butoxycarbonylamino-methylpyrrolidin-1-ylcarbonyl]propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (202) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[(2R)-2-tert-butoxycarbonylamino-methylpyrrolidin-1-ylcarbonyl]propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (203) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[(3R,S)-hydroxymethylpyrrolidin-1-yl)carbonyl]propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (204) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-(1,1-dioxo-1-thiomorpholine-4-ylcarbonyl]propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (205) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[(4-methyl-3-oxopiperazin-1-ylcarbonyl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (206) rac.-N-[(5-chloro-1H-benzimidazol-2-yl)-(4-chlorophenyl)methyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (207) rac.-N-[(5-chloro-1H-benzimidazol-2-yl)-(2-chlorophenyl)methyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (208) N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-methoxyethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (209) 3-chloro-N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-methoxyethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (210) 3-bromo-N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-27methoxyethyl]-4-(pyrrolidin-1-ylcarbonyl)benzamide, (211) 4-{(2R)-2-[2-(tert-butoxycarbonylamino)ethyl]pyrrolidin-1-ylcarbonyl}-3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]benzamide, (212) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[2-(2-ethoxycarbonylethyl)pyrrolidin-1-ylcarbonyl]benzamide, (213) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]1-{(2R)-2-[(3-ethyl-ureido)methyl]pyrrolidin-1-ylcarbonyl}benzamide, (214) 4-[(2R)-2-(2-aminoethyl)pyrrolidin-1-ylcarbonyl]-3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]benzamide, (215) 3-bromo-N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-methoxyethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (216) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(4,5,6,7-tetrahydrobenzimidazol-1-yl)-3-trifluoromethylbenzamide, (217) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[3-(ethoxycarbonyl)-5,6-dihydro-4H-cyclopentapyrazol-1-yl]-3-trifluoromethylbenzamide, (218) 4-[3-(tert-butoxycarbonylamino)methyl-5,6-dihydro-4H-cyclopentapyrazol-1-yl]-N-(5-chloro-1H-benzimidazol-2-ylmethyl)-3-trifluoromethylbenzamide, (219) rac.-4-[3-(aminocarbonyl)-5,6-dihydro-4H-cyclopentapyrazol-1-yl]-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-trifluoromethylbenzamide, (220) 4-(3-aminomethyl-5,6-dihydro-4H-cyclopentapyrazol-1-yl)-N-[(S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-trifluoromethylbenzamide, (221) 4-[3-(tert-butoxycarbonylamino)methyl-5,6-dihydro-4H-cyclopentapyrazol-1-yl]-N-[(1s)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-trifluoromethylbenzamide, (222) 4-(3-aminomethyl-5,6-dihydro-4H-cyclopentapyrazol-1-yl)-N-(5-chloro-1H-benzimidazol-2-ylmethyl)-3-trifluoromethylbenzamide, (223) 3-methyl-N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-hydroxyethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (224) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[(2S)-2-aminomethylpyrrolidin-1-ylcarbonyl]propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (225) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[(2R)-2-ainomethylpyrrolidin-1-ylcarbonyl]propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (226) N-(5-chloro-1H-indol-2-ylmethyl)-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (227) rac.-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(4-formylpiperazin-1-ylcarbonyl)benzamide, (228) rac.-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[N-ethyl-N-(piperidin-4-yl)aminocarbonyl]benzamide, (229) 3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[2-(2-dimethylaminoethyl)piperidin-1-ylcarbonyl]benzamide, (230) 3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[2-(piperidin-1-ylmethyl)piperidin-1-ylcarbonyl]benzamide, (231) 3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[2-(3-diethylaminopropyl)piperidin-1-ylcarbonyl]benzamide, (232) 4-[2-(N-butyl-N-ethylaminomethyl)piperidin-1-ylcarbonyl]-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]benzamide, (233) 3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[2-(N-cyclohexyl-N-methylaminomethyl)piperidin-1-ylcarbonyl]benzamide, (234) 3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(thiomorpholine-4-ylcarbonyl)benzamide, (235) 3-chloro-N-[(1R,S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[(2R)-2-methoxy-methylpyrrolidin-1-ylcarbonyl]benzamide, (236) rac.-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(1,4,6,7-tetrahydroimidazo[4,5-c]pyridin-5-ylcarbonyl)benzamide, (237) 3-chloro-N-[(1R,S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[(2S)-2-methoxy-methylpyrrolidin-1-ylcarbonyl]benzamide, (238) 4-(2-aminomethylpiperidin-1-ylcarbonyl)-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]benzamide, (239) 4-(3-aminomethylpiperidin-1-ylcarbonyl)-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]benzamide, (240) rac.-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-ylcarbonyl)benzamide, (241) 3-chloro-N-[(1R,S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[(2S)-2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-ylcarbonyl]benzamide, (242) 3-chloro-N-[(1R,S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[(2S)-2-(ethoxy-carbonyl)pyrrolidin-1-ylcarbonyl]benzamide, (243) 4-[3-(2-aminoethyl)piperidin-1-ylcarbonyl]-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]benzamide, (244) rac.-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(4-hydroxypiperazin-1-ylcarbonyl)benzamide, (245) 3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[2-(methyloxycarbonyl)pyrrolidin-1-ylcarbonyl]benzamide, (246) 4-[2-(benzyloxycarbonyl)pyrrolidin-1-ylcarbonyl]-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]benzamide, (247) 3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(3,4,5,6-tetrahydro-2H-[2,3]-bipyridinyl-1-ylcarbonyl)benzamide, (248) rac. 4-[N-(2-aminoethyl)-N-ethylameinocarbonyl]-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]benzamide, (249) rac.-4-[N-(3-aminopropyl)-N-ethylaminocarbonyl]-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]benzamide, (250) rac.-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(N-cyclopropyl-N-methylaminocarbonyl]benzamide, (251) rac.-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(2,5-dimethylpyrrolidin-1-ylcarbonyl)benzamide, (252) rac.-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(1,4,6,7-tetrahydropyrazol-[4,3-c]pyridin-5-ylcarbonyl)benzamide, (253) 3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[2-(pyridin-2-yl)pyrrolidin-1-ylcarbonyl]benzamide, (254) rac.-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[2-(pyridin-4-yl)pyrrolidin-1-ylcarbonyl]benzamide, (255) rac.-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(2,5-dimethyl-2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (256) 3-chloro-N-[(1R,S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[(2S)-2-phenylamino-methylpyrrolidin-1-ylcarbonyl]benzamide, (257) 4-(2-benzylpyrrolidin-1-ylcarbonyl)-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]benzamide, (258) 3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(2-phenethylpyrrolidin-1-ylcarbonyl)benzamide, (259) 3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(2-isopropylpyrrolidin-1-ylcarbonyl)benzamide, (260) 3-chloro-N-[(1R,S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[(2R)-2-phenylamino-methylpyrrolidin-1-ylcarbonyl]benzamide, (261) rac.-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(piperidin-1-ylcarbonyl)benzamide, (262) 3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(2-methylpiperidin-1-ylcarbonyl)benzamide, (263) rac.-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(4-hydroxypiperidin-1-ylcarbonyl)benzamide, (264) rac.-4-(4-acetylpiperazin-1-ylcarbonyl)-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]benzamide, (265) 3-chloro-N-[(1R,S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[(2R)-2-(ethoxycarbonyl)pyrrolidin-1-ylcarbonyl]benzamide, (266) rac.-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(4-oxopiperidin-1-ylcarbonyl)benzamide, (267) rac.-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-([1,4]-diazepan-1-ylcarbonyl)benzamide, (268) 3-chloro-N-[(1R,S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[(2S)-2-(dimethyl-aminocarbonyl)pyrrolidin-1-ylcarbonyl]benzamide, (269) 3-chloro-N-[(1R,S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[(2S)-2-(methyl-aminocarbonyl)pyrrolidin-1-ylcarbonyl]benzamide, (270) 4-[(2S)-2-(aminocarbonylmethylaminocarbonyl)pyrrolidin-1-ylcarbonyl]-3-chloro-N-[(1R,S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]benzamide, (271) 4-((2S)-2-benzhydrylpyrrolidin-1-ylcarbonyl)-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]benzamide, (272) rac.-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[3-(2,2,2-trifluoroacetyl-amino)pyrrolidin-1-ylcarbonyl]benzamide, (273) 3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(3-dimethylaminopyrrolidin-1-ylcarbonyl)benzamide, (274) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(imidazol-1-ylmethyl)-3-methoxybenzamide, (275) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methoxy-4-(2-oxopyrrolidin-1-ylmethyl)benzamide, (276) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methoxy-4-(3-oxopiperazin-1-ylmethyl)benzamide, (277) 3-bromo-N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-hydroxyethyl]-4-(pyrrolidin-1-ylcarbonyl)benzamide, (278) N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-methoxyethyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-trifluoromethylbenzamide, (279) N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-methoxyethyl]4-(pyrrolidin-1-ylcarbonyl)-3-trifluoromethylbenzamide, (280) 3-chloro-N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-isopropoxycarbonyloxyethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (281) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-(2-isopropylaminothiazol-4-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (282) N-[(1S)-1,3-bis-(5-chloro-1H-benzimidazol-2-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (283) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[(2S)-2-(ethoxycarbonylmethyl)pyrrolidin-1-ylcarbonyl]benzamide, (284) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[(2R/S)-2-dimethyl-aminomethylpyrrolidin-1-ylcarbonyl]benzamide, (285) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[(2S)-2-(hydroxy-carbonylmethyl)pyrrolidin-1-ylcarbonyl]benzamide, (286) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[(2R/S)-2-(hydroxy-carbonylethyl)pyrrolidin-1-ylcarbonyl]benzamide, (287) N-[(1S)-3-[1-(benzyloxycarbonyl)piperidin-4-yl]-1-(5-chloro-1H-benzimidazol-2-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (288) rac.-N-[(5-chloro-1H-benzimidazol-2-yl)thiophen-3-ylmethyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-methylbenzamide, (289) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methanesulfonylaminopropyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-methylbenzamide, (290) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-piperidin-4-ylpropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (291) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrol-1-ylcarbonyl)benzamide, (292) 3-bromo-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(thiazolidin-3-ylcarbonyl)benzamide, (293) 3-bromo-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[(2R/S)-2-methylpyrrolidin-1-ylcarbonyl]benzamide, (294) 3-bromo-4-[(2R/S)-2-(tert-butoxycarbonylaminomethyl)thiazolidin-3-ylcarbonyl]-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]benzamide, (295) N-[(1S)-1-(6-amino-5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (296) 4-[(2R/S)-2-aminomethylthiazolidin-3-ylcarbonyl]-3-bromo-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]benzamide, (297) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[N-ethyl-N-(6-methoxy-hexanoyl)amino]-3-methylbenzamide, (298) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[(3R/S)-3-fluoropyrrolidin-1-ylcarbonyl]-3-methylbenzamide, (299) N-[(1R)-2-benzyloxy-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-bromo-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (300) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)butyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-methylbenzamide, (301) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)butyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (302) 3-bromo-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)butyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (303) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[(2S)-2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-ylcarbonyl]benzamide, (304) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[(2R/S)-2-(2-pyrrolidin-1-ylcarbonylethyl)pyrrolidin-1-ylcarbonyl]benzamide, (305) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl] 4-[(2R)-2-(ethoxycarbonylmethyl)pyrrolidin-1-ylcarbonyl]benzamide, (306) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-methylbenzamide, (307) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (308) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[(2R/S)-2-(2-methyl-aminocarbonylethyl)pyrrolidin-1-ylcarbonyl]benzamide, (309) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[(2R)-2-(hydroxycarbonylmethyl)pyrrolidin-1-ylcarbonyl]benzamide, (310) 3-bromo-N-[(1S)-1-(5-bromo-1H-benzimidazol-2-yl)ethyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (311) N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-methylsulfanylethyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-methylbenzamide, (312) 4-(N-acetyl-N-cyclopentylamino)-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-methylsulfanylethyl]-3-methylbenzamide, (313) 4-(N-acetyl-N-cyclopentylamino)-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methylbenzamide, (314) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[(2R)-2-methylamino-carbonylmethylpyrrolidin-1-yl]benzamide, (315) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-trifluoromethylbenzamide, (316) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[(2R)-2-(imidazol-1-ylmethyl)pyrrolidin-1-ylcarbonyl]benzamide, (317) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-ylcarbonyl]benzamide, (318) 3-bromo-N-[(1R)-1-(5-bromo-1H-benzimidazol-2-yl)-2-methoxyethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (319) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)butyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)-2-trifluoromethylbenzamide, (320) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-(1,1-dioxoisothiazolidin-2-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (321) 3-bromo-N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-ethoxyethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (322) 3-chloro-N-[(1R,2R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-methoxypropyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (323) N-[(1R)-2-allyloxy-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-methylbenzamide, (324) N-[(1R,2S)-2-tert-butoxy-1-(5-chloro-1H-benzimidazol-2-yl)propyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-methylbenzamide, (325) N-[(1R,2S)-1-(5-chloro-1H-benziimidazol-2-yl)-2-hydroxypropyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-methylbenzamide, (326) 4-{(2R)-2-[(N-acetyl-N-methylamino)methyl]pyrrolidin-1-ylcarbonyl}-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-chloro-benzamide, (327) 4-benzoyl-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methylbenzamide, (328) 3-bromo-N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-prop-2-ynyloxyethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (329) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-(1H-tetrazol-5-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (330) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(3-methyl-5,6-dihydro-4H-cyclopentapyrazol-1-yl)-3-trifluoromethylbenzainide, (331) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(4-oxo-4,5,6,7-tetrahydroindol-1-yl)benzamide, (332) N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-hydroxyethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-trifluoromethylbenzamide, (333) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)but-3-ynyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (334) N-[(1S)-1-(5-hydroxy-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (335) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(4,5,6,7-tetrahydroindol-1-yl)benzamide, (336) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(4,5,6,7-tetrahydroindazol-1-yl)benzamide, (337) rac.-N-[1-(5-chloro-1H-indol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (338) rac.-N-[(5-chloro-1H-indol-2-yl)phenylmethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (339) rac.-3-chloro-N-[(5-chloro-1H-indol-2-yl)phenylmethyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (340) rac.-N-[3-chloro-4-(2,5-dihydropyrrol-1-ylcarbonyl)phenyl]-2-(5-chloro-1H-indol-2-yl)acetamide, (341) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfanylpropyl]-4-(4-oxo-2-propyl-4,5-dihydroimidazo[4,5-c]pyridin-1-yl)-3-trifluoromethylbenzamide, (342) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(2-methyl-5,6-dihydro-4H-cyclopentaimidazol-1-yl)-3-trifluoromethylbenzamide, (343) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(2-methyl-4,5,6,7-tetrahydrobenzimidazol-1-yl)-3-trifluoromethylbenzamide, (344) rac.-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[2-hydroxycarbonylmethyl-3-oxopiperazin-1-ylcarbonyl]benzamide, (345) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(4-methoxyimidazo[4,5-c]pyridin-1-yl)-3-trifluoromethylbenzamide, (346) rac.-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(2-hydroxycarbonylpyrrolidin-1-ylcarbonyl)benzamide, (347) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(2-dimethylaminomethylbenzimidazol-1-yl)-3-trifluoromethylbenzamide, (348) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(4-oxo-4,5-dihydroimidazo-[4,5-c]pyridin-1-yl)-3-trifluoromethylbenzamide, (349) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(2-dimethylaminomethyl-indol-1-yl)-3-trifluoromethylbenzamide, (350) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(4-oxo-4,5-dihydropyrrol-[3,2-c]pyridin-1-yl)-3-trifluoromethylbenzamide, (351) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(2-methyl-4,5,6,7-tetra-hydrobenzimidazol-1-yl)benzamide, (352) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(3-oxo-[1,4]diazepan-1-ylcarbonyl)benzamide, (353) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-5-[(5-oxopyrrolidin-3-yl)carbonylamino]pentyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (354) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-5-[(pyridin-3-yl-)carbonylamino]pentyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (355) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-5-[(5-oxopyrrolidin-2-yl)carbonylamino]pentyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (356) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-5-[(pyridin-4-yl)carbonylamino]pentyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (357) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-5-[(2S)-(1-methylpyrrolidin-2-yl)carbonylamino]pentyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (358) 2-(5-chloro-1H-indol-2-yl)-N-[3-methyl-4-(pyrrolidin-1-ylcarbonyl)phenyl]pent-4-enoic acid amide, (359) N-[(1R)-2-benzyloxy-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (360) N-[(1R)-2-(acetylaminomethylsulfanyl)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (361) N-[(1s)-3-aminocarbonyl-1-(5-chloro-1H-benzimidazol-2-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (362) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-(1H-indol-3-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (363) rac.-N-[-1-(5-chloro-1H-benzimidazol-2-yl)-2-(4-hydroxy-3,5-dimethylphenyl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (364) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-methoxycarbonylethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (365) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(4-hydroxy-2,6-dimethylphenyl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (366) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(4-difluoromethoxyphenyl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (367) rac.-N-[2-(3-bromophenyl)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (368) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-(4-trifluoromethylphenyl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (369) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-5-ureidopentyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (370) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-5-ureidobutyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (371) rac.-N-[2-(4-amino-3,5-dibromophenylcarbonyl)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (372) N-[(1S)-2-allyloxycarbonyl-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (373) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-(3,4-dimethoxyphenyl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (374) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-(thiazol-4-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (375) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-(3,5-difluorophenyl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (376) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-(4-fluorophenyl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (377) N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-mercaptoethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (378) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-(1-methyl-1H-imidazol-5-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (379) rac.-N-[1-(5-chlor-6-1H-benzimidazol-2-yl)-2-(1H-benzimidazol-5-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (380) rac.-N-[(5-chloro-1H-benzimidazol-2-yl)thiophen-3-ylmethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (381) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-(thiophen-3-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (382) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)but-3-enyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (383) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-(4-chlorophenyl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (384) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-cyclopropylethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (385) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[2-(pyrrolidin-1-yl)-methyl-5,6-dihydro-4H-cyclopentaimidazol-1-yl]benzamide, (386) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[2-(2-(pyrrolidin-1-yl)-ethyl)-5,6-dihydro-4H-cyclopentaimidazol-1-yl])benzamide, (387) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[2-(pyrrolidin-1-yl)-methyl-4,5,6,7-tetrahydrobenzimidazol-1-yl]benzamide, (388) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[2-(2-pyrrolidin-1-ylethyl)4,5,6,7-tetrahydrobenzimidazol-1-yl]benzamide, (389) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[2-(morpholin-4-yl)-methyl-5,6-dihydro-4H-cyclopentaimidazol-1-yl]benzamide, (390) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[2-(2-(morpholin-4-yl)-ethyl)-5,6-dihydro-4H-cyclopentaimidazol-1-yl]benzamide, (391) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[2-(morpholin-4-yl)-methyl-4,5,6,7-tetrahydrobenzimidazol-1-yl]benzamide, (392) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[2-(2-(morpholin-4-yl)-ethyl)-4,5,6,7-tetrahydrobenzimidazol-1-yl]benzamide, (393) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(2-oxohexahydrocyclopentaimidazol-1-yl)benzamide, (394) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(4-oxo-4,5,6,7-tetrahydropyrrol[3,2-c]pyridin-1-yl)-3-trifluoromethylbenzamide, (395) 3-chloro-N-[(S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(4-oxooctahydropyrrol[3,2-c]pyridin-1-yl)benzamide, (396) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(octahydrocyclopenta-pyrazin-1-yl)benzamide, (397) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(2,3-dioxooctahydrocyclopentapyrazin-1-yl)benzamide, (398) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(2-oxo-2,5,6,7-tetrahydrocyclopentapyrazin-1-yl)benzamide, (399) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(5,6,7,7a-tetrahydro-1H-pyrrol-[1,2-c]-imidazol-3-yl)benzamide, (400) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(3,4,4a,5,6,7-hexahydropyrrol-[1,2-c]pyrimidin-1-yl)-3-methylbenzamide, (401) N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-(2,2,2-trifluoroethoxy)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (402) N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-trifluoromethoxyethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (403) N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-difluoromethoxyethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (404) N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-fluoromethoxyethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (405) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-((2R)-2-dimethylamino-methylpyrrolidin-1-ylcarbonyl)benzamide, (406) 3-chloro-N-[(1R)-1-(5-bromo-1H-benzimidazol-2-yl)-2-hydroxyethyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (407) 3-bromo-N-[(1R)-1-(5-bromo-1H-benzimidazol-2-yl)-2-hydroxyethyl]4-(pyrrolidin-1-ylcarbonyl)benzamide, and (408) 3-methyl-N-[(1R)-1-(5-bromo-1H-benzimidazol-2-yl)-2-hydroxyethyl]-4-(pyrrolidin-1-ylcarbonyl)benzamide, and the tautomers and salts thereof.
 15. A compound selected from: (1) N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (2) N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (3) N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-ethyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (4) (S)-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(pyridin-4-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (5) (S)-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-(1H-imidazol-4-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (6) N-[1-(5-chloro-H-benzimidazol-2-yl)ethyl]-3-chloro-4-(2-aminomethylpyrrolidin-1-ylcarbonyl)benzamide, (7) 3-chlor-6-N-(5-chloro-1H-benzimidazol-2-ylmethyl)-4-(2-methylpyrrolidin-1-ylcarbonyl)benzamide, (8) N-[1-(5-bromo-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (9) N-[(5-chloro-1H-benzimidazol-2-yl)phenylmethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (10) N-[1-(5-chloro-1H-benzimidazol-2-yl)-5-benzyloxycarbonylaminopentyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (11) N-[1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-chloro-4-(3-oxopiperazin-1-ylcarbonyl)benzamide, (12) (S)-N-[1-(5-chloro-1H-benzimidazol-2-yl)]ethyl-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (13) N-[1-(5-chloro-1H-benzimidazol-2-yl)]ethyl-3-bromo-4-(pyrrolidin-1-ylcarbonyl)benzamide, (14) N-[1-(5-chloro-1H-benzimidazol-2-yl)]ethyl-3-trifluoromethyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (15) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-[(2R/S)-2-amino-methylpyrrolidin-1-ylcarbonyl]benzamide, (16) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-chloro-4-[(2R/S)-2-aminomethylpyrrolidin-1-ylcarbonyl)benzamide, (17) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-chloro-4-[(2S)-2-aminomethylpyrrolidin-1-ylcarbonyl]benzamide, (18) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-chloro-4-[(2R)-2-aminomethylpyrrolidin-1-ylcarbonyl]benzamide, (19) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-chloro-4-[(2S)-2-(2-aminoethyl)pyrrolidin-1-ylcarbonyl]benzamide, (20) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfanylpropyl]-3-chloro-4-[(2S)-2-(N-tert-butoxycarbonylaminomethyl)pyrrolidin-1-ylcarbonyl]benzamide, (21) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)butyl]-3-chloro-4-[(2S)-2-aminomethylpyrrolidin-1-ylcarbonyl]benzamide, (22) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfonylpropyl]-3-chloro-4-[(2S)-2-(N-tert-butoxycarbonylaminomethyl)pyrrolidin-1-ylcarbonyl]benzamide, (23) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfanylpropyl]-3-chloro-4-[(2S)-2-aminomethylpyrrolidin-1-ylcarbonyl]benzamide, (24) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfinylpropyl]-3-chloro-4-[(2S)-2-aminomethylpyrrolidin-1-ylcarbonyl]benzamide, (25) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfonylpropyl]-3-chloro-4-[(2S)-2-aminomethylpyrrolidin-1-ylcarbonyl]benzamide, (26) N-[(1S)-5-(benzyloxycarbonylamino)-1-(5-chloro-1H-benzimidazol-2-yl)pentyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (27) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-phenylpropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (28) N-[(1S)-5-acetylamino-1-(5-chloro-1H-benzimidazol-2-yl)pentyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (29) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfanylpropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (30) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-hydroxyethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (31) rac.-N-[2-acetylamino-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (32) rac.-N-[2-benzoylamino-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl 4-(pyrrolidin-1-ylcarbonyl)benzamide, (33) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-3-hydroxycarbonylpropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (34) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-hydroxycarbonylpropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (35) rac.-N-[3-benzyloxycarbonyl-1-(5-chloro-1H-benzimidazol-2-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (36) N-[(1S)-3-benzyloxycarbonyl-1-(5-chloro-1H-benzimidazol-2-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (37) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-3-ethylaminocarbonylpropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (38) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-3-(pyrrolidin-1-ylcarbonyl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (39) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-(pyrrolidin-1-ylcarbonyl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (40) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-3-diethylaminocarbonylpropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (41) N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-hydroxyethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (42) N-[(1R,2R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-hydroxypropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (43) N-[(1S)-2-acetylamino-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (44) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-methylsulfonylaminoethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (45) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-methoxyethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (46) 3-bromo-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-ethyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (47) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methoxypropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (48) N-[(1s)-4-acetylamino-1-(5-chloro-1H-benzimidazol-2-yl)butyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (49) rac.-N-[(5-chloro-1H-benzimidazol-2-yl)-(3-chlorophenyl)methyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (50) N-[(1R)-2-(C-tert-butoxycarbonylmethyloxy)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (51) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(3-oxopiperazin-1-ylcarbonyl)benzamide, (52) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfinylpropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (53) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfonylpropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (54) rac.-N-[1-(5-chloro-1H-benzimidazol-2-yl)phenylmethyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-methylbenzamide, (55) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (56) N-[(1S)-3-(benzyloxycarbonylamino)-1-(5-chloro-1H-benzimidazol-2-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (57) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfonylaminopropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (58) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-(2-oxoimidazolidin-1-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (59) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[3-(2-chloroethyl)ureido]propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (60) 3-chloro-N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-ethylsulfanylethyl]4-(pyrrolidin-1-ylcarbonyl)benzamide, (61) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)butyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (62) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-hydroxypropyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (63) 3-bromo-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfanylpropyl]4-(pyrrolidin-1-ylcarbonyl)benzamide, (64) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-(methylsulfanyl)propyl]4-(pyrrolidin-1-ylcarbonyl)benzamide, (65) 3-bromo-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-(methylsulfonyl)propyl]4-(pyrrolidin-1-ylcarbonyl)benzamide, (66) 3-bromo-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methylsulfinylpropyl]-4-(pyrrolidin-1-ylcarbonyl)benzamide, (67) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[(2R,S)-(2-methylpyrrolidin-1-ylcarbonyl)]benzamide, (68) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[(2R)-2-(methyl-sulfonylaminomethyl)pyrrolidin-1-ylcarbonyl]benzamide, (69) (1R)-3-bromo-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-hydroxyethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (70) (1R)-3-methyl-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-methoxyethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (71) (1R)-3-chloro-N-[1-(5-chloro-1H-benzimidazol-2-yl)-2-hydroxyethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (72) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3r-(pyridin-4-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (73) N-[(1S)-3-(benzyloxycarbonylamino)-1-(5-chloro-1H-benzimidazol-2-yl)propyl]-3-methyl-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (74) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[(3R,S-3-dimethylaminopyrrolidin-1-yl]carbonylpropyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (75) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[(3R)-3-hydroxypyrrolidin 1-yl]carbonylpropyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (76) N-{(1S)-1-(5-chloro-H-benzimidazol-2-yl)-3-[(35)-3-hydroxypyrrolidin-1-ylcarbonyl]propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (77) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[(2R)-2-hydroxymethylpyrrolidin-1-ylcarbonyl]propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (78) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[(2S)-2-hydroxymethylpyrrolidin-1-ylcarbonyl]propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (79) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-(2-methyl-2,6-diazaspiro[3.4]oct-6-ylcarbonyl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (80) N-{(1S)-3-[(1S)-2-(aminocarbonyl)pyrrolidin-1-ylcarbonyl]-1-(5-chloro-1H-benzimidazol-2-yl)propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (81) N-{(1S)-3-[(1R)-2-(aminocarbonyl)pyrrolidin-1-ylcarbonyl]-1-(5-chloro-1H-benzimidazol-2-yl)propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (82) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[(2S)-2-tert-butoxycarbonylamino-methylpyrrolidin-1-ylcarbonyl]propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (83) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[(2R)-2-tert-butoxycarbonylamino-methylpyrrolidin-1-ylcarbonyl]propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (84) N-{(1) 1-(5-chloro-1H-benzimidazol-2-yl)-3-[(3R,S)-hydroxymethylpyrrolidin-1-yl)carbonyl]propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (85) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-(1,1-dioxo-1-thiomorpholine-4-ylcarbonyl]propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (86) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[(4-methyl-3-oxopiperazin-1-ylcarbonyl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (87) N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-methoxyethyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (88) 3-chloro-N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-methoxyethyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (89) 3-bromo-N-[(1R)-1-(5-chloro-H-benzimidazol-2-yl)-2-methoxyethyl]4-(pyrrolidin-1-ylcarbonyl)benzamide, (90) 4-[(2R)-2-(2-aminoethyl)pyrrolidin-1-ylcarbonyl]-3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]benzamide, (91) 3-bromo-N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-methoxyethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (92) 4-(3-aminomethyl-5,6-dihydro-4H-cyclopentapyrazol-1-yl)-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-3-trifluoromethylbenzamide, (93) 3-methyl-N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-hydroxyethyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (94) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[(2S)-2-aminomethylpyrrolidin-1-ylcarbonyl]propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (95) N-{(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-[(2R)-2-aminomethylpyrrolidin-1-ylcarbonyl]propyl}-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (96) 3-bromo-N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-hydroxyethyl]-4-(pyrrolidin-1-ylcarbonyl)benzamide, (97) N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-methoxyethyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-trifluoromethylbenzamide, (98) N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-methoxyethyl]-4-(pyrrolidin-1-ylcarbonyl)-3-trifluoromethylbenzamide, (99) N-[(S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-(2-isopropylaminothiazol-4-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (100) N-[(1S)-1,3-bis-(5-chloro-1H-benzimidazol-2-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (101) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-[(2R/S)-2-dimethyl-aminomethylpyrrolidin-1-ylcarbonyl]benzamide, (102) rac.-N-[(5-chloro-1H-benzimidazol-2-yl)thiophen-3-ylmethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-methylbenzamide, (103) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-methanesulfonylaminopropyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-methylbenzamide, (104) 3-bromo-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(thiazolidin-3-ylcarbonyl)benzamide, (105) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)butyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-methylbenzamide, (106) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)butyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (107) 3-bromo-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)butyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (108) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-methylbenzamide, (109) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (110) 3-bromo-N-[(1S)-1-(5-bromo-1H-benzimidazol-2-yl)ethyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (111) 4-(N-acetyl-N-cyclopentylamino)-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-2-methylsulfanylethyl]-3-methylbenzamide, (112) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-trifluoromethylbenzamide, (113) 3-chloro-N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]4-[(2R)-2-(pyrrolidin-1-ylmethyl)pyrrolidin-1-ylcarbonyl]benzamide, (114) 3-bromo-N-[(1R)-1-(5-bromo-1H-benzimidazol-2-yl)-2-methoxyethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (115) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-(1,1-dioxoisothiazolidin-2-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, (116) 3-bromo-N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-ethoxyethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (117) N-[(1R)-2-allyloxy-1-(5-chloro-1H-benzimidazol-2-yl)ethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-methylbenzamide, (118) 3-bromo-N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-prop-2-ynyloxyethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)benzamide, (119) N-[(1S)-1-(5-chloro-1H-benzimidazol-2-yl)-3-(1H-tetrazol-5-yl)propyl]-3-methyl-4-(pyrrolidin-1-ylcarbonyl)benzamide, and (120) N-[(1R)-1-(5-chloro-1H-benzimidazol-2-yl)-2-hydroxyethyl]-4-(2,5-dihydropyrrol-1-ylcarbonyl)-3-trifluoromethylbenzamide, the tautomers and salts thereof.
 16. The physiologically acceptable salts of a compound according to one of claims 1 to
 15. 17. A pharmaceutical composition comprising a compound according to one of claims 1 to 15 or a physiologically acceptable salt thereof and one or more inert carriers and/or diluents. 